The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.展开更多
There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,...There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
BACKGROUND Liver cirrhosis(LC)affect millions of people worldwide.The pathogenesis of cirrhosis involves complex interactions between immune responses and gut microbiota.Recent studies have highlighted the role of the...BACKGROUND Liver cirrhosis(LC)affect millions of people worldwide.The pathogenesis of cirrhosis involves complex interactions between immune responses and gut microbiota.Recent studies have highlighted the role of the interleukin-36(IL-36)subfamily in inflammation and immune regulation.However,the relationship between serum IL-36 subfamily levels and gut microbiota in cirrhosis patients remains unclear.This study aimed to explore the clinical significance of serum IL-36 subfamily levels and their association with gut microbiota in cirrhosis patients.AIM To explore the clinical significance of serum IL-36 subfamily levels and their relationship with gut microbiota among cirrhosis patients.METHODS Sixty-one cirrhosis patients were enrolled from Lihuili Hospital of Ningbo University from May 2022 to November 2023 as the LC group and 29 healthy volunteers as the healthy control(HC)group.The serum expressions of IL-36α,IL-36β, IL-36γ, IL-36Ra, and IL-38 were measured through ELISA, while 16S rRNA gene sequencing was employed torate microbial community in human fecal samples.RESULTSThe serum levels of IL-36α, IL-36γ, IL-36Ra, and IL-38 in the LC group remarkably exceeded those in the HC group(P < 0.05). IL-36α, IL-36γ, and IL-38 were related positively to the Child-Pugh score (P < 0.05) and prominentlyexceeded those in the Child-Pugh C group (P < 0.05). The absolute abundance of harmful bacteria (Bacteroides,Bifidobacterium, Faecalibacterium) remarkably rose, while the beneficial bacteria (Firmicutes, Bacteroides, Escherichia-Shigella) notably decreased in the LC group (P < 0.05). IL-36α, IL-36γ, and IL-38 related positively to Lactobacillus(P < 0.05), while IL-38 negatively related to Fusicatenibacter (P < 0.05).CONCLUSIONIL-36γ and IL-38 show promise as potential biomarkers for LC progression, but further validation is required.展开更多
Crohn’s disease(CD)is a chronic inflammatory disorder characterized by dysregulated immune responses and significant disruption of intestinal immunity.A recent case-control study by Andreu-Ballester et al revealed de...Crohn’s disease(CD)is a chronic inflammatory disorder characterized by dysregulated immune responses and significant disruption of intestinal immunity.A recent case-control study by Andreu-Ballester et al revealed decreased expression of interleukin(IL)-2 receptor subunitγ(CD132)in CD tissues,a finding that has profound implications for understanding immune dysregulation in CD.CD132,an essential component of the IL-7/IL-2 signaling axis,is critical forγδT cell survival and function,which are pivotal for maintaining gut integrity and modulating inflammation.Here,we propose that reduced CD132 expression represents a key mechanism underlyingγδT cell deficiencies in CD,contributing to impaired immune surveillance and exacerbated inflammation.This hypothesis integrates emerging evidence from cytokine signaling and immunopathology in CD,offering new insights into its pathogenesis.These findings highlight the therapeutic potential of targeting the IL-7/IL-2 axis to restore immune homeostasis in CD,presenting a novel avenue for future research and intervention.展开更多
Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneu...Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneumonia who were diagnosed and treated in the hospital from May 2024 to May 2025.The expression level of IL-17D in the serum of all patients was recorded.Patients were divided into severe and mild groups based on their disease severity.Gender,age,disease duration,presence of fever,atelectasis,pneumothorax,interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),and interleukin-17D were selected as independent variables.Statistical software SPSS 22.00 was used for univariate analysis,and variables with statistical significance in the univariate analysis were included in a multivariate logistic regression analysis to determine the correlation between IL-17D and the severity of severe pneumonia.Results:The results of this study showed that the level of IL-17D in patients with severe pneumonia was significantly higher than the normal threshold.Univariate analysis indicated that atelectasis,IL-2,IL-6,and IL-17D were statistically significant(P<0.05)and could be considered as influencing factors for the severity of severe pneumonia.Multivariate logistic regression analysis revealed that atelectasis(OR=2.141,95%CI:1.684–2.391),IL-2(OR=2.884,95%CI:2.240–3.614),IL-6(OR=2.571,95%CI:2.190–2.943),and IL-17D(OR=2.416,95%CI:2.093–2.735)were positively correlated with the severity of severe pneumonia.Conclusion:The expression level of IL-17D in the serum of patients with severe pneumonia is higher than the normal threshold and is positively correlated with disease severity.展开更多
BACKGROUND Hypertension is a chronic cardiovascular disease characterized by persistently elevated arterial blood pressure.It is not only a significant risk factor for cardio-vascular and cerebrovascular diseases(such...BACKGROUND Hypertension is a chronic cardiovascular disease characterized by persistently elevated arterial blood pressure.It is not only a significant risk factor for cardio-vascular and cerebrovascular diseases(such as myocardial infarction and stroke)but also closely related to multiple organ damages(such as kidney disease and retinopathy),imposing a heavy health and economic burden on individuals and society.AIM To investigate the expression differences and relationships of endothelin-1(ET-1),interleukin-6(IL-6),stem cell factor(SCF),and its receptor(c-kit)in hypertensive patients with or without depression.METHODS A retrospective analysis was conducted on the clinical data of 163 hypertensive patients admitted to our hospital from March 2022 to January 2024.Based on the presence of depression,patients were divided into Group A(n=77,with depre-ssion)and Group B(n=86,without depression).Serum levels of ET-1 and IL-6 were measured using radioimmunoassay,while serum levels of SCF and c-kit were measured using ELISA.The differences in ET-1,IL-6,SCF,and c-kit levels between Groups A and B were compared.Additionally,the differences in these biomarkers among patients with varying degrees of depression in Group A were analyzed.Pearson correlation analysis was used to examine the relationship between ET-1,IL-6,SCF,c-kit levels,and Hamilton depression rating scale(HAMD)scores.Multivariate logistic regression analysis was performed to identify factors influencing hypertension with depression.The diagnostic efficacy of individual and combined biomarkers was analyzed using receiver operating characteristic(ROC)curves.Comparative statistical analysis of the area under the curve(AUC)values was performed using DeLong’s test to assess the superiority of combined biomarker detection.RESULTS The levels of ET-1 and IL-6 in Group A were significantly higher than those in Group B,while the levels of SCF and c-kit were significantly lower in Group A compared to Group B(P<0.05).In the severe depression subgroup,ET-1 and IL-6 levels were higher than those in the mild-to-moderate depression subgroup,while SCF and c-kit levels were lower(P<0.05).Pearson correlation analysis showed that ET-1 and IL-6 levels were positively correlated with HAMD scores(r=0.442,0.463,P<0.05),while SCF and c-kit levels were negatively correlated with HAMD scores(r=-0.429,-0.394,P<0.05).Multivariate logistic regression analysis revealed that high ET-1,high IL-6,low SCF,and low c-kit were independent influencing factors for hypertension with depression(P<0.05).ROC analysis revealed AUCs of 0.746(ET-1),0.801(IL-6),0.732(SCF),0.779(c-kit),and 0.884(combination).The combined diagnosis demonstrated significantly higher AUC than individual markers(DeLong's test,P<0.01),with superior sensitivity(90.24%)and specificity(85.37%).CONCLUSION Compared to patients with hypertension alone,patients with hypertension and depression exhibited higher serum levels of ET-1 and IL-6 and lower levels of SCF and c-kit.High ET-1,high IL-6,low SCF,and low c-kit were inde-pendent influencing factors for hypertension with depression.The combination of ET-1,IL-6,SCF,and c-kit demonstrated significant diagnostic value for hypertension with depression.展开更多
BACKGROUND Acute pancreatitis(AP)is a potentially life-threatening complication of pancreaticoduodenectomy that increases morbidity and mortality in patients.Interleukin-17A(IL-17a)the potential preoperative marker fo...BACKGROUND Acute pancreatitis(AP)is a potentially life-threatening complication of pancreaticoduodenectomy that increases morbidity and mortality in patients.Interleukin-17A(IL-17a)the potential preoperative marker for predicting postoperative outcomes.The purpose of this study is to retrospectively assess the prognostic value of preoperative IL-17a level in prediction of AP and related postoperative pancreatic fistula(POPF)following pancreaticoduodenectomy.AIM To retrospectively assess the prognostic value of preoperative IL-17a levels in predicting AP and related POPF following pancreaticoduodenectomy.METHODS Retrospective analysis of pancreaticoduodenectomies performed on patients 150 patients between 2017 and 2023.Clinical data including pre-operative IL-17a levels were collected.The primary composite outcomes were postoperative AP and postoperative pancreatic(PP),and the predictive performances of IL-17a levels and fluid load status for postoperative complications were evaluated by statistical analysis.RESULTS A total of 150 patients were included,and 26 patients(17.3%)developed postoperative AP and 34 patients(22.7%)developed PP.Preoperative IL-17a was a risk factor for postoperative AP(P=0.03).Furthermore,excessive intraoperative fluid load was a significantly associated(P=0.01)with PP.The model(IL-17a levels+fluid load status)was highly accurate.CONCLUSION Preoperative IL-17a levels and intravascular volume status may serve as useful predictors of AP and subsequent PP following PD.These parameters provide means to evaluate preoperative risk and may guide clinical decision making to enhance postoperative recovery.展开更多
Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines w...Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance.By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines(A549/DDP and SK-MES-1/DDP),the authors show that increased levels of interleukin(IL)-6,IL-8,and tumor necrosis factor-αare linked to resistance.Logistic regression identifies IL-6 and IL-8 as key risk factors.Functional experiments using tocilizumab,an IL-6 receptor antagonist,demonstrate a reduction in DDP half maximum inhibitory concentration,higher apoptosis rates,and decreased migration and invasion in resistant cells.Although the study has certain limitations,such as the analysis of only five inflammatory cytokines in a small,non-stratified patient cohort;it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance.Overall,the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.展开更多
BACKGROUND Interleukin-22(IL-22)belongs to the IL-10 cytokine family,recognized for its ability to modulate diverse immune responses.Previous studies have indicated that IL-22 promotes cancer advancement and metastasi...BACKGROUND Interleukin-22(IL-22)belongs to the IL-10 cytokine family,recognized for its ability to modulate diverse immune responses.Previous studies have indicated that IL-22 promotes cancer advancement and metastasis.However,the precise function of IL-22 in colorectal cancer(CRC)remains unclear.AIM To investigate the role of IL-22 in promoting stem cell-like characteristics and chemotherapy resistance in CRC cells,as well as to elucidate the mechanisms underlying these effects.METHODS HCT116 cells were treated with IL-22(50 ng/mL)and oxaliplatin(L-OHP,5μg/mL).A series of functional assays-including cell counting kit-8 assay,tumor sphere formation assay,and cell apoptosis assay-were conducted to assess the effects of IL-22 on cell viability and stem cell-like characteristics.The expression of stemness-related markers(SOX2,Oct4,NANOG,and Bmi-1)was examined using Western blot analysis.Additionally,the total and phosphorylated levels of epidermal growth factor receptor(EGFR),protein kinase B(AKT),and extracellular signal-regulated kinase(ERK)were evaluated by Western blot.An EGFR inhibitor,osimertinib(Osi),was used to assess the pathway's functional relevance.RESULTS IL-22 treatment promotes CRC cell proliferation,enhances sphere formation,and elevates the expression of stem cell markers,including SOX2,Oct4,NANOG,and Bmi-1.IL-22 treatment increases the phosphorylation of EGFR,AKT,and ERK.Additionally,IL-22 treatment mitigates the cytotoxic effects and the ability to induce apoptosis of L-OHP.Furthermore,IL-22 treatment activated the EGFR/ERK signaling pathway by increasing the phosphorylation of EGFR,AKT,and ERK.Importantly,the use of the EGFR inhibitor Osi significantly counteracted the chemoresistance induced by IL-22 in CRC cells.CONCLUSION IL-22 promotes tumor growth and induces chemotherapy resistance in CRC cells by activating the EGFR/ERK signaling pathway.These findings suggest that targeting IL-22 or its downstream signaling may offer novel therapeutic strategies in CRC.展开更多
In this letter,we discuss the recently published study by Pan et al,which invest-igated the relationships between interleukin-36(IL-36)subfamily cytokines and the gut microbiota in patients diagnosed with liver cirrho...In this letter,we discuss the recently published study by Pan et al,which invest-igated the relationships between interleukin-36(IL-36)subfamily cytokines and the gut microbiota in patients diagnosed with liver cirrhosis.This observational study revealed that the serum levels of IL-36α,IL-36γ,and IL-38 were significantly elevated in liver cirrhosis patients,accompanied by a distinct gut microbiota profile.These findings provide novel insights into the role of inflammatory cytokines in the imbalance of the gut-liver axis.Meanwhile,in our studies,it was found that IL-36γis considerably increased in a mouse model of metabolic dys-function-associated liver disease,which may be linked to the activation of T helper type 17 cells and macrophages.Thus,this letter provides a brief introdu-ction to the role of IL-36 in liver diseases and anticipates further studies aimed at elucidating the full potential of IL-36 in the development of liver diseases.展开更多
Intestinal inflammation is a common challenge in intensive aquaculture,yet its pathogenesis remains unclear.While interleukin 22(IL-22)is recognized as a critical regulator of cellular homeostasis during inflammation ...Intestinal inflammation is a common challenge in intensive aquaculture,yet its pathogenesis remains unclear.While interleukin 22(IL-22)is recognized as a critical regulator of cellular homeostasis during inflammation in higher vertebrates,its roles in fish are not well understood.This study established hypoxia-induced models in intestinal tissues and primary intestinal epithelial cells of yellow catfish to investigate the involvement of IL-22 in maintaining intestinal homeostasis.Results revealed that Pelteobagrus fulvidraco IL-22(Pf_IL-22)was abundantly expressed in mucosal tissues,with the highest levels in the gill and intestine.Hypoxia induced pronounced intestinal injury,characterized by loosening of the lamina propria and extensive vacuolization,while activating hypoxia-inducible factor(HIF)signaling and markedly up-regulating IL-22 expression.IL-22 levels peaked at 24 h post-hypoxia,suggesting a role in early immune responses.Recombinant Pf_IL-22 also induced transcription of pro-inflammatory mediators,including IL-1βand tumor necrosis factorα(TNF-α),in primary intestinal epithelial cells,indicating a dual regulatory function in balancing protection and inflammation.Mechanistic analyses revealed that HIF-1αdirectly interacted with a hypoxia response element within the IL-22 promoter to drive transcription,as confirmed by dual-luciferase assays,electrophoretic mobility-shift assays,and HIF-1αknockdown.Silencing Pf_IL-22 significantly suppressed Th17 cell differentiation pathways,demonstrating its role in shaping downstream immune responses.These findings establish the HIF-1α/IL-22 axis as a key regulatory pathway modulating immune responses and alleviating intestinal inflammation,providing a basis for developing IL-22-targeted immunotherapies and selective breeding strategies in aquaculture.展开更多
High mobility group box 1(HMGB1),when released extracellularly,plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system.In experimental auto...High mobility group box 1(HMGB1),when released extracellularly,plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system.In experimental autoimmune encephalomyelitis(EAE),a condition that models multiple sclerosis,the levels of extracellular HMGB1 and interleukin-33(IL-33)have been found to be inversely correlated.However,the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive.Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes,upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice.Conversely,the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes.These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.展开更多
Interleukin-1 receptor-associated kinase 4(IRAK4)is a key kinase downstream of the interleukin-1 receptor(IL-1R)and Toll-like receptors(TLRs)signaling pathway,whose overexpression and hyperactivation have been associa...Interleukin-1 receptor-associated kinase 4(IRAK4)is a key kinase downstream of the interleukin-1 receptor(IL-1R)and Toll-like receptors(TLRs)signaling pathway,whose overexpression and hyperactivation have been associated with several inflammatory diseases or cancer.Therefore,targeting IRAK4 has emerged as a promising therapeutic strategy.A range of potent and selective IRAK4 inhibitors and degraders based on draggability have been designed and developed.This article provides a comprehensive summary of the IRAK4 inhibitors and degraders that have been developed and discusses the challenges and opportunities for research in this area.展开更多
Type 1 diabetes(T1D)is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells,which ultimately results in insulinopenia,hyperglycemia and lifelo...Type 1 diabetes(T1D)is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells,which ultimately results in insulinopenia,hyperglycemia and lifelong need for exogenous insulin therapy.In the pathophysiological landscape of T1D,T helper 17 cells(Th17 cells)and their hallmark cytokine,interleukin(IL)-17,play pivotal roles from disease onset to disease progression.In this narrative mini-review,we discuss the dynamic interplay between Th17 cells and IL-17 in the context of T1D,providing insights into the underlying immunologic mechanisms contributing to the IL-17-immunity-mediated pancreatic beta-cell destruction.Furthermore,we summarized the main animal and clinical studies that investigated Th17-and IL-17-targeted interventions as promising immunotherapies able to alter the natural history of T1D.展开更多
[Objective] The study aimed to clone interleukin-2(IL-2) gene from Sichuan white goose. [Method] Based on the IL-2 gene of duck accessed in GenBank, a pair of primers was designed for cloning IL-2 gene from total RNA ...[Objective] The study aimed to clone interleukin-2(IL-2) gene from Sichuan white goose. [Method] Based on the IL-2 gene of duck accessed in GenBank, a pair of primers was designed for cloning IL-2 gene from total RNA of peripheral blood lymphocytes of Sichuan white goose stimulated by ConA via RT-PCR technology. The yielded fragment was sequenced for bioinformatics analysis. [Result] The full length of IL-2 gene of Sichuan white goose is 468 bp that contains a 441 bp open reading frame(ORF), encoding 146 amino acid residues. Bioinformatics analysis shows that the amino acid sequence of IL-2 gene of Sichuan white goose contains four phosphorylation sites, a glycosylation site and a signal peptide with 21 amino acid residues. Homologies of IL-2 nucleotide sequence and amino acid sequence between Sichuan white goose and duck, chicken, turkey are 92.7%, 77.5%, 78.2% and 85.8%, 65.5%, 64.1%, respectively. By contrast IL-2 nucleotide sequence and amino acid sequence between Sichuan white goose and mammalian and rodents such as human, monkey, rat, bovine, horse, pig, cat, mouse, rabbit and deer, are all less than 45% and 28%, respectively. [Conclusion] The IL-2 gene of Sichuan white goose has closer genetic relationship with those of chicken and duck.展开更多
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
基金supported by the National Natural Science Foundation of China(No.82170326 and No.82470328 to Y.D.,No.82100339 to Q.D.).
文摘Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.
文摘There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
基金Supported by Key Project of the Ningbo Natural Science Foundation,Zhejiang Province,China,No.2022J253Key Technology R&D Project of Ningbo City,No.2023Z208+1 种基金Traditional Chinese Medicine project,Zhejiang Province,No.2024ZF028the Key Project of Health Science and Technology Foundation,Zhejiang Province,China,No.WKJ-ZJ-2551.
文摘BACKGROUND Liver cirrhosis(LC)affect millions of people worldwide.The pathogenesis of cirrhosis involves complex interactions between immune responses and gut microbiota.Recent studies have highlighted the role of the interleukin-36(IL-36)subfamily in inflammation and immune regulation.However,the relationship between serum IL-36 subfamily levels and gut microbiota in cirrhosis patients remains unclear.This study aimed to explore the clinical significance of serum IL-36 subfamily levels and their association with gut microbiota in cirrhosis patients.AIM To explore the clinical significance of serum IL-36 subfamily levels and their relationship with gut microbiota among cirrhosis patients.METHODS Sixty-one cirrhosis patients were enrolled from Lihuili Hospital of Ningbo University from May 2022 to November 2023 as the LC group and 29 healthy volunteers as the healthy control(HC)group.The serum expressions of IL-36α,IL-36β, IL-36γ, IL-36Ra, and IL-38 were measured through ELISA, while 16S rRNA gene sequencing was employed torate microbial community in human fecal samples.RESULTSThe serum levels of IL-36α, IL-36γ, IL-36Ra, and IL-38 in the LC group remarkably exceeded those in the HC group(P < 0.05). IL-36α, IL-36γ, and IL-38 were related positively to the Child-Pugh score (P < 0.05) and prominentlyexceeded those in the Child-Pugh C group (P < 0.05). The absolute abundance of harmful bacteria (Bacteroides,Bifidobacterium, Faecalibacterium) remarkably rose, while the beneficial bacteria (Firmicutes, Bacteroides, Escherichia-Shigella) notably decreased in the LC group (P < 0.05). IL-36α, IL-36γ, and IL-38 related positively to Lactobacillus(P < 0.05), while IL-38 negatively related to Fusicatenibacter (P < 0.05).CONCLUSIONIL-36γ and IL-38 show promise as potential biomarkers for LC progression, but further validation is required.
文摘Crohn’s disease(CD)is a chronic inflammatory disorder characterized by dysregulated immune responses and significant disruption of intestinal immunity.A recent case-control study by Andreu-Ballester et al revealed decreased expression of interleukin(IL)-2 receptor subunitγ(CD132)in CD tissues,a finding that has profound implications for understanding immune dysregulation in CD.CD132,an essential component of the IL-7/IL-2 signaling axis,is critical forγδT cell survival and function,which are pivotal for maintaining gut integrity and modulating inflammation.Here,we propose that reduced CD132 expression represents a key mechanism underlyingγδT cell deficiencies in CD,contributing to impaired immune surveillance and exacerbated inflammation.This hypothesis integrates emerging evidence from cytokine signaling and immunopathology in CD,offering new insights into its pathogenesis.These findings highlight the therapeutic potential of targeting the IL-7/IL-2 axis to restore immune homeostasis in CD,presenting a novel avenue for future research and intervention.
基金Chongqing Shapingba District Technology Innovation Project(Project No.:2024046)。
文摘Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneumonia who were diagnosed and treated in the hospital from May 2024 to May 2025.The expression level of IL-17D in the serum of all patients was recorded.Patients were divided into severe and mild groups based on their disease severity.Gender,age,disease duration,presence of fever,atelectasis,pneumothorax,interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),and interleukin-17D were selected as independent variables.Statistical software SPSS 22.00 was used for univariate analysis,and variables with statistical significance in the univariate analysis were included in a multivariate logistic regression analysis to determine the correlation between IL-17D and the severity of severe pneumonia.Results:The results of this study showed that the level of IL-17D in patients with severe pneumonia was significantly higher than the normal threshold.Univariate analysis indicated that atelectasis,IL-2,IL-6,and IL-17D were statistically significant(P<0.05)and could be considered as influencing factors for the severity of severe pneumonia.Multivariate logistic regression analysis revealed that atelectasis(OR=2.141,95%CI:1.684–2.391),IL-2(OR=2.884,95%CI:2.240–3.614),IL-6(OR=2.571,95%CI:2.190–2.943),and IL-17D(OR=2.416,95%CI:2.093–2.735)were positively correlated with the severity of severe pneumonia.Conclusion:The expression level of IL-17D in the serum of patients with severe pneumonia is higher than the normal threshold and is positively correlated with disease severity.
文摘BACKGROUND Hypertension is a chronic cardiovascular disease characterized by persistently elevated arterial blood pressure.It is not only a significant risk factor for cardio-vascular and cerebrovascular diseases(such as myocardial infarction and stroke)but also closely related to multiple organ damages(such as kidney disease and retinopathy),imposing a heavy health and economic burden on individuals and society.AIM To investigate the expression differences and relationships of endothelin-1(ET-1),interleukin-6(IL-6),stem cell factor(SCF),and its receptor(c-kit)in hypertensive patients with or without depression.METHODS A retrospective analysis was conducted on the clinical data of 163 hypertensive patients admitted to our hospital from March 2022 to January 2024.Based on the presence of depression,patients were divided into Group A(n=77,with depre-ssion)and Group B(n=86,without depression).Serum levels of ET-1 and IL-6 were measured using radioimmunoassay,while serum levels of SCF and c-kit were measured using ELISA.The differences in ET-1,IL-6,SCF,and c-kit levels between Groups A and B were compared.Additionally,the differences in these biomarkers among patients with varying degrees of depression in Group A were analyzed.Pearson correlation analysis was used to examine the relationship between ET-1,IL-6,SCF,c-kit levels,and Hamilton depression rating scale(HAMD)scores.Multivariate logistic regression analysis was performed to identify factors influencing hypertension with depression.The diagnostic efficacy of individual and combined biomarkers was analyzed using receiver operating characteristic(ROC)curves.Comparative statistical analysis of the area under the curve(AUC)values was performed using DeLong’s test to assess the superiority of combined biomarker detection.RESULTS The levels of ET-1 and IL-6 in Group A were significantly higher than those in Group B,while the levels of SCF and c-kit were significantly lower in Group A compared to Group B(P<0.05).In the severe depression subgroup,ET-1 and IL-6 levels were higher than those in the mild-to-moderate depression subgroup,while SCF and c-kit levels were lower(P<0.05).Pearson correlation analysis showed that ET-1 and IL-6 levels were positively correlated with HAMD scores(r=0.442,0.463,P<0.05),while SCF and c-kit levels were negatively correlated with HAMD scores(r=-0.429,-0.394,P<0.05).Multivariate logistic regression analysis revealed that high ET-1,high IL-6,low SCF,and low c-kit were independent influencing factors for hypertension with depression(P<0.05).ROC analysis revealed AUCs of 0.746(ET-1),0.801(IL-6),0.732(SCF),0.779(c-kit),and 0.884(combination).The combined diagnosis demonstrated significantly higher AUC than individual markers(DeLong's test,P<0.01),with superior sensitivity(90.24%)and specificity(85.37%).CONCLUSION Compared to patients with hypertension alone,patients with hypertension and depression exhibited higher serum levels of ET-1 and IL-6 and lower levels of SCF and c-kit.High ET-1,high IL-6,low SCF,and low c-kit were inde-pendent influencing factors for hypertension with depression.The combination of ET-1,IL-6,SCF,and c-kit demonstrated significant diagnostic value for hypertension with depression.
文摘BACKGROUND Acute pancreatitis(AP)is a potentially life-threatening complication of pancreaticoduodenectomy that increases morbidity and mortality in patients.Interleukin-17A(IL-17a)the potential preoperative marker for predicting postoperative outcomes.The purpose of this study is to retrospectively assess the prognostic value of preoperative IL-17a level in prediction of AP and related postoperative pancreatic fistula(POPF)following pancreaticoduodenectomy.AIM To retrospectively assess the prognostic value of preoperative IL-17a levels in predicting AP and related POPF following pancreaticoduodenectomy.METHODS Retrospective analysis of pancreaticoduodenectomies performed on patients 150 patients between 2017 and 2023.Clinical data including pre-operative IL-17a levels were collected.The primary composite outcomes were postoperative AP and postoperative pancreatic(PP),and the predictive performances of IL-17a levels and fluid load status for postoperative complications were evaluated by statistical analysis.RESULTS A total of 150 patients were included,and 26 patients(17.3%)developed postoperative AP and 34 patients(22.7%)developed PP.Preoperative IL-17a was a risk factor for postoperative AP(P=0.03).Furthermore,excessive intraoperative fluid load was a significantly associated(P=0.01)with PP.The model(IL-17a levels+fluid load status)was highly accurate.CONCLUSION Preoperative IL-17a levels and intravascular volume status may serve as useful predictors of AP and subsequent PP following PD.These parameters provide means to evaluate preoperative risk and may guide clinical decision making to enhance postoperative recovery.
文摘Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance.By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines(A549/DDP and SK-MES-1/DDP),the authors show that increased levels of interleukin(IL)-6,IL-8,and tumor necrosis factor-αare linked to resistance.Logistic regression identifies IL-6 and IL-8 as key risk factors.Functional experiments using tocilizumab,an IL-6 receptor antagonist,demonstrate a reduction in DDP half maximum inhibitory concentration,higher apoptosis rates,and decreased migration and invasion in resistant cells.Although the study has certain limitations,such as the analysis of only five inflammatory cytokines in a small,non-stratified patient cohort;it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance.Overall,the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.
文摘BACKGROUND Interleukin-22(IL-22)belongs to the IL-10 cytokine family,recognized for its ability to modulate diverse immune responses.Previous studies have indicated that IL-22 promotes cancer advancement and metastasis.However,the precise function of IL-22 in colorectal cancer(CRC)remains unclear.AIM To investigate the role of IL-22 in promoting stem cell-like characteristics and chemotherapy resistance in CRC cells,as well as to elucidate the mechanisms underlying these effects.METHODS HCT116 cells were treated with IL-22(50 ng/mL)and oxaliplatin(L-OHP,5μg/mL).A series of functional assays-including cell counting kit-8 assay,tumor sphere formation assay,and cell apoptosis assay-were conducted to assess the effects of IL-22 on cell viability and stem cell-like characteristics.The expression of stemness-related markers(SOX2,Oct4,NANOG,and Bmi-1)was examined using Western blot analysis.Additionally,the total and phosphorylated levels of epidermal growth factor receptor(EGFR),protein kinase B(AKT),and extracellular signal-regulated kinase(ERK)were evaluated by Western blot.An EGFR inhibitor,osimertinib(Osi),was used to assess the pathway's functional relevance.RESULTS IL-22 treatment promotes CRC cell proliferation,enhances sphere formation,and elevates the expression of stem cell markers,including SOX2,Oct4,NANOG,and Bmi-1.IL-22 treatment increases the phosphorylation of EGFR,AKT,and ERK.Additionally,IL-22 treatment mitigates the cytotoxic effects and the ability to induce apoptosis of L-OHP.Furthermore,IL-22 treatment activated the EGFR/ERK signaling pathway by increasing the phosphorylation of EGFR,AKT,and ERK.Importantly,the use of the EGFR inhibitor Osi significantly counteracted the chemoresistance induced by IL-22 in CRC cells.CONCLUSION IL-22 promotes tumor growth and induces chemotherapy resistance in CRC cells by activating the EGFR/ERK signaling pathway.These findings suggest that targeting IL-22 or its downstream signaling may offer novel therapeutic strategies in CRC.
基金Supported by National Natural Science Foundation of China,No.82104549.
文摘In this letter,we discuss the recently published study by Pan et al,which invest-igated the relationships between interleukin-36(IL-36)subfamily cytokines and the gut microbiota in patients diagnosed with liver cirrhosis.This observational study revealed that the serum levels of IL-36α,IL-36γ,and IL-38 were significantly elevated in liver cirrhosis patients,accompanied by a distinct gut microbiota profile.These findings provide novel insights into the role of inflammatory cytokines in the imbalance of the gut-liver axis.Meanwhile,in our studies,it was found that IL-36γis considerably increased in a mouse model of metabolic dys-function-associated liver disease,which may be linked to the activation of T helper type 17 cells and macrophages.Thus,this letter provides a brief introdu-ction to the role of IL-36 in liver diseases and anticipates further studies aimed at elucidating the full potential of IL-36 in the development of liver diseases.
基金supported by the National Natural Science Foundation of China(32102760)“JBGS”Project of Seed Industry Revitalization in Jiangsu Province(JBGS(2021)034)+1 种基金Creation Project of Major New Species of Agriculture in Jiangsu Province(PZCZ201742)Key Laboratory of Healthy Freshwater Aquaculture,Ministry of Agriculture and Rural Affairs,Key Laboratory of Freshwater Aquaculture Genetic and Breeding of Zhejiang Province,Zhejiang Institute of Freshwater Fisheries,Huzhou 313001(ZJK202404)。
文摘Intestinal inflammation is a common challenge in intensive aquaculture,yet its pathogenesis remains unclear.While interleukin 22(IL-22)is recognized as a critical regulator of cellular homeostasis during inflammation in higher vertebrates,its roles in fish are not well understood.This study established hypoxia-induced models in intestinal tissues and primary intestinal epithelial cells of yellow catfish to investigate the involvement of IL-22 in maintaining intestinal homeostasis.Results revealed that Pelteobagrus fulvidraco IL-22(Pf_IL-22)was abundantly expressed in mucosal tissues,with the highest levels in the gill and intestine.Hypoxia induced pronounced intestinal injury,characterized by loosening of the lamina propria and extensive vacuolization,while activating hypoxia-inducible factor(HIF)signaling and markedly up-regulating IL-22 expression.IL-22 levels peaked at 24 h post-hypoxia,suggesting a role in early immune responses.Recombinant Pf_IL-22 also induced transcription of pro-inflammatory mediators,including IL-1βand tumor necrosis factorα(TNF-α),in primary intestinal epithelial cells,indicating a dual regulatory function in balancing protection and inflammation.Mechanistic analyses revealed that HIF-1αdirectly interacted with a hypoxia response element within the IL-22 promoter to drive transcription,as confirmed by dual-luciferase assays,electrophoretic mobility-shift assays,and HIF-1αknockdown.Silencing Pf_IL-22 significantly suppressed Th17 cell differentiation pathways,demonstrating its role in shaping downstream immune responses.These findings establish the HIF-1α/IL-22 axis as a key regulatory pathway modulating immune responses and alleviating intestinal inflammation,providing a basis for developing IL-22-targeted immunotherapies and selective breeding strategies in aquaculture.
基金supported by the National Natural Science Foundation of China(82001281 and 82371195)Hubei Provincial Natural Science Foundation of China for Distinguished Young Scholars(2022CFA104)the Research Fund of Jianghan University(2022XKZX28).
文摘High mobility group box 1(HMGB1),when released extracellularly,plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system.In experimental autoimmune encephalomyelitis(EAE),a condition that models multiple sclerosis,the levels of extracellular HMGB1 and interleukin-33(IL-33)have been found to be inversely correlated.However,the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive.Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes,upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice.Conversely,the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes.These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
基金supported by the National Natural Science Foundation of China(Nos.82293684,82293680)the National Key R&D Program of China(No.2020YFA0908004)CAMS Innovation Fund for Medical Science of China(No.2022-I2M-1-014)。
文摘Interleukin-1 receptor-associated kinase 4(IRAK4)is a key kinase downstream of the interleukin-1 receptor(IL-1R)and Toll-like receptors(TLRs)signaling pathway,whose overexpression and hyperactivation have been associated with several inflammatory diseases or cancer.Therefore,targeting IRAK4 has emerged as a promising therapeutic strategy.A range of potent and selective IRAK4 inhibitors and degraders based on draggability have been designed and developed.This article provides a comprehensive summary of the IRAK4 inhibitors and degraders that have been developed and discusses the challenges and opportunities for research in this area.
基金Supported by the European Union-NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘Type 1 diabetes(T1D)is a chronic organ-specific autoimmune disorder characterized by a progressive loss of the insulin-secreting pancreatic beta cells,which ultimately results in insulinopenia,hyperglycemia and lifelong need for exogenous insulin therapy.In the pathophysiological landscape of T1D,T helper 17 cells(Th17 cells)and their hallmark cytokine,interleukin(IL)-17,play pivotal roles from disease onset to disease progression.In this narrative mini-review,we discuss the dynamic interplay between Th17 cells and IL-17 in the context of T1D,providing insights into the underlying immunologic mechanisms contributing to the IL-17-immunity-mediated pancreatic beta-cell destruction.Furthermore,we summarized the main animal and clinical studies that investigated Th17-and IL-17-targeted interventions as promising immunotherapies able to alter the natural history of T1D.
文摘[Objective] The study aimed to clone interleukin-2(IL-2) gene from Sichuan white goose. [Method] Based on the IL-2 gene of duck accessed in GenBank, a pair of primers was designed for cloning IL-2 gene from total RNA of peripheral blood lymphocytes of Sichuan white goose stimulated by ConA via RT-PCR technology. The yielded fragment was sequenced for bioinformatics analysis. [Result] The full length of IL-2 gene of Sichuan white goose is 468 bp that contains a 441 bp open reading frame(ORF), encoding 146 amino acid residues. Bioinformatics analysis shows that the amino acid sequence of IL-2 gene of Sichuan white goose contains four phosphorylation sites, a glycosylation site and a signal peptide with 21 amino acid residues. Homologies of IL-2 nucleotide sequence and amino acid sequence between Sichuan white goose and duck, chicken, turkey are 92.7%, 77.5%, 78.2% and 85.8%, 65.5%, 64.1%, respectively. By contrast IL-2 nucleotide sequence and amino acid sequence between Sichuan white goose and mammalian and rodents such as human, monkey, rat, bovine, horse, pig, cat, mouse, rabbit and deer, are all less than 45% and 28%, respectively. [Conclusion] The IL-2 gene of Sichuan white goose has closer genetic relationship with those of chicken and duck.
