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
OBJECTIVE:To identify the main active ingredients of Improved Yupingfeng Powder prescription(IYPFP,玉屏风散加味)and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins(OVA)-induced allerg...OBJECTIVE:To identify the main active ingredients of Improved Yupingfeng Powder prescription(IYPFP,玉屏风散加味)and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins(OVA)-induced allergic rhinitis(AR)in mice.METHODS:Bagg Albino/substrain mice were sensitized with OVA emulsified in aluminum hydroxide adjuvant,followed by intranasal challenge to establish AR models.Treatment groups received IYPFP(1.5 or 4.5 g/kg)via daily gavage for 14 d.The nasal mucosa tissues were collected for pathological observation.The expression of OVA-specific immunoglobulin E(Ig E),histamine,and interleukin-33(IL-33)was detected by enzyme-linked immunosorbent assay.IL-5,IL-13,IL-33,suppression of tumorigenicity 2(ST2),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)in the nasal mucosa and lung were detected by quantitative polymerase chain reaction and Western blot.High performance liquid chromatography and ultra-high performance liquid chromatography quadrupole exactive orbitrap mass spectrometry were used to detect the chemical fingerprints of IYPFP,and the chemical compositions of plasma from rats treated with IYPFP at 0.5,1,1.5,2,3,4 and 6 h,respectively.Virtual screening of bioactive compounds was conducted through molecular docking targeting IL-33/ST2 pathway proteins.RESULTS:Eight chemical compounds of IYPFP were accurately identified,they are prim-O-glucosylcimifugin(peak 2),calycosin-7-O-β-D-glucoside(peak 4),cimifugin(peak 5),5-O-methylvisammioside(peak 6),sec-Oglucosylhamaudol(peak 12),calycosin(peak 15),formononetin(peak 19),and magnolin(peak 21).Compared with the OVA model group,IYPFP alleviated the nasal symptoms,improved nasal mucosal injury and downregulated the levels of OVA-specific Ig E,histamine and IL-33.Additionally,IYPFP reduced the levels of IL-5,IL-13,TNF-α,IL-33,and ST2 in the lungs,but upregulated IFN-γ.Molecular docking confirmed that eight representative compounds of IYPFP had good binding properties with IL-5,IL-13,IFN-γ,histamine,IL-33 and ST2,and were able to inhibit the activation of the IL33/ST2 inflammatory pathway.CONCLUSION:This study demonstrates that IYPFP ameliorates AR by modulating IL-33/ST2 pathway which provides a theoretical basis for the clinical treatment of patients with AR.展开更多
Interleukin-33 （IL-33）, a newly recognized IL-1 family member, is expressed by various tissues and cells. Since it can combine with chromosomes, IL-33 is regarded as an intracellular transcription repressor. Upon pr...Interleukin-33 （IL-33）, a newly recognized IL-1 family member, is expressed by various tissues and cells. Since it can combine with chromosomes, IL-33 is regarded as an intracellular transcription repressor. Upon proinflammatory stimulation, it is released as an extracellular cytokine to function as an alarmin to dangerous signals. The IL-33 receptor is a heterodimer complex composed of ST2 and the IL-1 receptor accessory protein, the latter being conserved in other IL-1 family members. The IL-33/ST2 signaling pathway plays critical roles in inflammatory and immune diseases, as well as in central nervous system （CNS） diseases. Recently, there has been an increasing focus on IL-33, particularly on its production and functions in the CNS. The present review mainly focuses on progress in research on IL-33, especially its roles in the CNS.展开更多
Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of mo...Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of molecules called alarmins may be involved in sterile brain inflammation,and we have already reported the potential impact of interleukin-33(IL-33)on positive symptoms onset and the role of its soluble trans-membranes full length receptor(sST2)on amelioration of negative symptoms in schizophrenia genesis.Furthermore,these molecules have already been shown to be involved in breast cancer etiopathogenesis.In this review article,we aim to describe the IL-33/suppressor of tumorigenicity 2(ST2)axis as a crossroad in schizophreniabreast cancer comorbidity.Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33,these selective estrogen receptor modulators could be useful in complementary treatment.These observations could guide further somatic,as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.展开更多
BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor pool.Safe utilization of these extended criteria grafts is paramount...BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor pool.Safe utilization of these extended criteria grafts is paramount given the increased risk associated with their use in transplantation.Prognostic factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are lacking.AIM To understand the relationship between interleukin-33(IL-33)and complement in recipients immediately following liver reperfusion as a marker of liver dysfunction.METHODS Cohort consisted of patients who received a liver transplant from September 2016–September 2019 at our institution.Clinical variables were retrospectively extracted from the electronic medical record.Back-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a boardcertified pathologist.Blood samples were available immediately following liver transplantation.Quantification of plasma IL-33 and complement proteins,C3a and C5a,were determined by enzyme-linked immunosorbent assay.For mRNA expression,RNA was extracted from donor biopsies and used against a 780 gene panel.RESULTS Cohort consisted of 99 donor and recipients.Donor median age was 45 years and 55%male.Recipients had a median age of 59 years with 62%male.The main etiologies were alcoholic hepatitis,nonalcoholic steatohepatitis,and hepatocellular carcinoma.Median MELD-Na at transplant was 21.Donors were grouped based on moderate macrosteatosis(≥30%).Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase(P<0.001 and P<0.004),and increased incidence of early allograft dysfunction(60%compared to 18%).Circulating IL-33 levels were significantly elevated in recipients of≥30%macrosteatotic grafts(P<0.05).Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly higher alanine aminotransferase/aspartate aminotransferase(P<0.05 and P<0.01).Activated complement(C3a and C5a)were elevated in recipients implanted with moderate macrosteatotic grafts.RNA expression analysis of donor biopsies revealed moderate steatotic grafts upregulated genes inflammatory processes while downregulated hepatocyte-produced complement factors.CONCLUSION Circulating IL-33 and activated complement levels immediately following liver reperfusion in recipients of moderate macrosteatotic grafts may identify which patients are at risk of early allograft dysfunction.展开更多
Interleukin (IL) 33 is a key cytokine in type II immune and airway diseases. It is abundantly expressed in lung epithelial cells and plays an important role in both innate and adaptive immunity. In innate immunity, IL...Interleukin (IL) 33 is a key cytokine in type II immune and airway diseases. It is abundantly expressed in lung epithelial cells and plays an important role in both innate and adaptive immunity. In innate immunity, IL-33 responds promptly to produce an immune response that maintains homeostasis. In adaptive immunity, IL-33 interacts with various immune cells. At the same time, IL-33 also plays an important role in chronic inflammation of the airway and its remodeling. This article reviews the relevant biological knowledge of IL-33 and its research progress in lung immunity, and discusses the related issues of IL-33 as a lung immune test site and therapeutic target.展开更多
Objective:To determine the involvement and the modulatory effects of IL-33 during Plasmodium berghei ANKA(PbA)infection.Methods:PbA infection in male ICR mice was utilized as a model of malaria.Systemically circulatin...Objective:To determine the involvement and the modulatory effects of IL-33 during Plasmodium berghei ANKA(PbA)infection.Methods:PbA infection in male ICR mice was utilized as a model of malaria.Systemically circulating IL-33 levels were determined in blood plasma by enzyme-linked immunosorbent assay(ELISA).After 24 hours post-inoculation of PbA,recombinant IL-33 and ST2,and antibodies against IL-33 and IgG treatments were administered daily for 3 days.Tissue expression and localization of IL-33 were assessed in organs generally affected by malaria via immunohistochemistry.Moreover,histopathological examination was performed to assess the effects of the treatments.Results:The levels of systemic IL-33 were elevated at the critical phase of PbA infection.Likewise,immunohistochemical analysis revealed a significant upregulation of IL-33 expression at the critical phase in the brain,lungs,and spleen of PbA-infected mice as compared to healthy controls.Treatment with IL-33 protected against experimental cerebral malaria development and reduced pathological features in the brain and lungs of the PbA-infected mice.Conclusions:A potential critical role and involvement of IL-33 in PbA infection may hint at the resolution of immunopathological sequelae associated with malaria.展开更多
Objective:To investigate the effects of rhubarb enema on the expression of inflammatory factors and interleukin-33(IL-33)and its prognosis in patients with SAP complicated with sepsis.Methods:A total of 47 patients wi...Objective:To investigate the effects of rhubarb enema on the expression of inflammatory factors and interleukin-33(IL-33)and its prognosis in patients with SAP complicated with sepsis.Methods:A total of 47 patients with SAP complicated with ARDS admitted to the Department of Critical Care Medicine,the First Affiliated Hospital of Chongqing Medical University from June 2016 to December 2018 were randomly divided into SAP with ARDS sepsis group(sepsis group)and SAP.In the ARDS non-sepsis group(non-sepsis group),20 patients were treated according to the guidelines for the diagnosis and treatment of acute pancreatitis in China in 2013.They were given regular fasting,gastrointestinal decompression,fluid resuscitation,acid suppression,and growth.On the basis of the inhibition of water,electrolytes,acid-base balance,add rhubarb 3 g/kg,water 200 mL,filter the slag juice to 37~38℃for retention enema for more than 15min,2 times a day For a total of 7 days.The inflammatory markers WBC,PCT,heart rate,respiratory rate,oxygenation index(PaO2/FiO2),pancreatic severity score(BISAP),and IL-33 and various cytokine changes were recorded in the two groups.Results:On the first day of admission,the patients in the sepsis group had more severe inflammation index(WBC:14.23±2.95,PCT:3.62±2.04,heart rate:104.02±8.89,respiration:26.81±2.44),and the oxygenation index was more.Poor(PaO2/FiO2:164.08±21.05),IL-33(46.32±7.82)and higher cytokine expression(TNF-α:266.78±72.89,IL-1:53.47±10.52,IL-6:1824.68±598.53,IL-8:160.42±50.34),the difference was statistically significant compared with the non-sepsis group,P<0.01.After the treatment of rhubarb enema,the above indicators were significantly decreased in both groups,and admission.The difference was statistically significant on the first day,P<0.01.However,on the seventh day after treatment,the sepsis patients hadΔIL-33(41.63±7.86)and cytokines(ΔTNF-α:258.90±72.18,ΔIL-1:47.87±11.85,ΔIL-6:1775.57±598.31,ΔIL-8:143.12±51.98),oxygenation index(162.01±43.23)improved better than non-sepsis group,P<0.01,and the rate of invasive ventilation was not statistically significant.P>0.05.Conclusion:SAP combined with sepsis leads to the use of rhubarb enema in patients with ARDS to significantly improve the concentration of IL-33 as a"target"factor and reduce the proinflammatory factors TNF-α,IL-1,IL-6 and IL-8.Level,improve the patient's oxygenation,has clinical application value.展开更多
Colorectal cancer(CRC)is presently the second most prevalent global mortalityinducing cancer.CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment.In addition...Colorectal cancer(CRC)is presently the second most prevalent global mortalityinducing cancer.CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment.In addition,non-neoplastic cell activities within tumor microenvironments for CRC development have been established.However,interleukin(IL)-33,secreted by such cell types,plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment.IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity(ST)2 receptor.Therefore,how to coordinate tumor microenvironment,design and optimize treatment strategies suitable for CRC,based on IL-33/ST2 signal is a challenge.Even though it has established influences upon immunitylinked conditions,IL-33 effects on CRC progression and prevention and related mechanisms are still controversial.Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention.Moreover,IL-33/ST2 signaling is a potential therapeutic target for CRC.展开更多
Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increa...Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.展开更多
目的:分析白细胞介素-33(interleukin-33,IL-33)在不同程度支气管哮喘患者中的变化及其与气道重塑的剂量-反应关系。方法:回顾性分析2022年5月至2024年5月于本院接受治疗的150例支气管哮喘患者的临床资料,根据疾病程度将所有患者分为重...目的:分析白细胞介素-33(interleukin-33,IL-33)在不同程度支气管哮喘患者中的变化及其与气道重塑的剂量-反应关系。方法:回顾性分析2022年5月至2024年5月于本院接受治疗的150例支气管哮喘患者的临床资料,根据疾病程度将所有患者分为重度组(81例)、中度组(46例)和轻度组(23例)。根据气道面积/总横截面积比值(airway area to total cross-sectional area ratio,WA)将所有患者分为气道重塑组(WA≥60%,57例)和非气道重塑组(WA<60%,93例)。比较不同疾病程度支气管哮喘患者的临床资料及IL-33变化。分析IL-33水平与支气管哮喘患者气道重塑指标的相关性。广义可加模型分析疾病程度与相关因素的关系。采用多因素logistic回归分析确定支气管哮喘患者气道重塑的独立风险预测因子。通过限制性立方样条模型评估IL-33水平与气道重塑的剂量-反应关系。采用受试工作者特征曲线分析IL-33水平对气道重塑的预测价值。结果:重度哮喘患者的IL-33、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)水平明显升高,金属蛋白抑制剂-1(tissue inhibitor of metalloprotein inhibitors-1,TIMP-1)水平明显降低(P<0.05)。IL-33水平MMP-9、TGF-β1呈正相关,与TIMP-1呈负相关(P<0.05)。多因素logistic回归分析结果显示,呼吸道感染、吸烟、嗜酸性粒细胞计数>1.55%、TIMP-1≤112.09µg/L、MMP-9>7.34 ng/mL、TGF-β1>3.77 ng/mL、白细胞介素-17>16.03 ng/L、IL-33>790.02 ng/L、重度哮喘均为影响支气管哮喘患者气道重塑的独立危险因素(P<0.05)。限制性立方样条模型结果显示,IL-33水平与气道重塑的关联强度呈非线性剂量反应关系(P<0.05)。IL-33水平对气道重塑具有一定的预测价值(曲线下面积=0.767)。结论:重度哮喘患者的IL-33水平明显升高,且IL-33水平是支气管哮喘患者气道重塑的重要影响因素,与患者气道重塑呈非线性剂量-反应关系。展开更多
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National Natural Science Foundation of China:Exploring the Mechanism of Improved Yupingfeng Powder in Treating Allergic Rhinitis Based on the Nucleotide-Binding Oligomerization Domain,Leucine-rich Repeat and Pyrin Domain-containing Protein 3/Interleukin-33-Mediated Activation Pathway of Pulmonary Group 2 Innate Lymphoid Cells in Airway Epithelial Cells(No.82374526)Science and Technology Project of Guangzhou:Mechanism of Shikonin in Treating Acute Lung Injury Through Regulating M1 Macrophage Polarization via Adenosine 5'-monophosphate-Activated Protein Kinase/Dynamin-Related Protein 1-mediated Mitochondrial Dynamics(No.2024A04J4334)+2 种基金Exemplary Study on Process Optimization and Quality Standard Enhancement of Hospital Preparations Such as Gangmei Qingyan Mixture(No.2023A03J0299)Anti-Allergic Mechanism of Improved Yupingfeng Powder in Alleviating Nasal Mucosal Inflammation in Allergic Rhinitis via Interleukin-33/Suppression of Tumorigenicity 2-Regulated Group 2 Innate Lymphoid Cells Suppression(No.202201020457)Elite Talent Program of the First Affiliated Hospital of Guangzhou University of Chinese Medicine by 2023 Years and Guangdong Province Lingnan Characteristic Hospital Preparation Transformation Engineering Technology Research Center(No.2023A170)。
文摘OBJECTIVE:To identify the main active ingredients of Improved Yupingfeng Powder prescription(IYPFP,玉屏风散加味)and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins(OVA)-induced allergic rhinitis(AR)in mice.METHODS:Bagg Albino/substrain mice were sensitized with OVA emulsified in aluminum hydroxide adjuvant,followed by intranasal challenge to establish AR models.Treatment groups received IYPFP(1.5 or 4.5 g/kg)via daily gavage for 14 d.The nasal mucosa tissues were collected for pathological observation.The expression of OVA-specific immunoglobulin E(Ig E),histamine,and interleukin-33(IL-33)was detected by enzyme-linked immunosorbent assay.IL-5,IL-13,IL-33,suppression of tumorigenicity 2(ST2),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)in the nasal mucosa and lung were detected by quantitative polymerase chain reaction and Western blot.High performance liquid chromatography and ultra-high performance liquid chromatography quadrupole exactive orbitrap mass spectrometry were used to detect the chemical fingerprints of IYPFP,and the chemical compositions of plasma from rats treated with IYPFP at 0.5,1,1.5,2,3,4 and 6 h,respectively.Virtual screening of bioactive compounds was conducted through molecular docking targeting IL-33/ST2 pathway proteins.RESULTS:Eight chemical compounds of IYPFP were accurately identified,they are prim-O-glucosylcimifugin(peak 2),calycosin-7-O-β-D-glucoside(peak 4),cimifugin(peak 5),5-O-methylvisammioside(peak 6),sec-Oglucosylhamaudol(peak 12),calycosin(peak 15),formononetin(peak 19),and magnolin(peak 21).Compared with the OVA model group,IYPFP alleviated the nasal symptoms,improved nasal mucosal injury and downregulated the levels of OVA-specific Ig E,histamine and IL-33.Additionally,IYPFP reduced the levels of IL-5,IL-13,TNF-α,IL-33,and ST2 in the lungs,but upregulated IFN-γ.Molecular docking confirmed that eight representative compounds of IYPFP had good binding properties with IL-5,IL-13,IFN-γ,histamine,IL-33 and ST2,and were able to inhibit the activation of the IL33/ST2 inflammatory pathway.CONCLUSION:This study demonstrates that IYPFP ameliorates AR by modulating IL-33/ST2 pathway which provides a theoretical basis for the clinical treatment of patients with AR.
基金supported by the National Natural Science Foundation of China(No.31000495,30970975,30821002)Research Fund for the Doctoral Program of Higher Education of China(No.20100071120046,20100071120042)+1 种基金the Fundamental Research Funds for the Central UniversitiesYoung Scientist Foundation of Fudan University,China
文摘Interleukin-33 （IL-33）, a newly recognized IL-1 family member, is expressed by various tissues and cells. Since it can combine with chromosomes, IL-33 is regarded as an intracellular transcription repressor. Upon proinflammatory stimulation, it is released as an extracellular cytokine to function as an alarmin to dangerous signals. The IL-33 receptor is a heterodimer complex composed of ST2 and the IL-1 receptor accessory protein, the latter being conserved in other IL-1 family members. The IL-33/ST2 signaling pathway plays critical roles in inflammatory and immune diseases, as well as in central nervous system （CNS） diseases. Recently, there has been an increasing focus on IL-33, particularly on its production and functions in the CNS. The present review mainly focuses on progress in research on IL-33, especially its roles in the CNS.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia(NO.175069)Faculty of Medical Sciences,University of Kragujevac(NO.JP15-05).
文摘Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of molecules called alarmins may be involved in sterile brain inflammation,and we have already reported the potential impact of interleukin-33(IL-33)on positive symptoms onset and the role of its soluble trans-membranes full length receptor(sST2)on amelioration of negative symptoms in schizophrenia genesis.Furthermore,these molecules have already been shown to be involved in breast cancer etiopathogenesis.In this review article,we aim to describe the IL-33/suppressor of tumorigenicity 2(ST2)axis as a crossroad in schizophreniabreast cancer comorbidity.Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33,these selective estrogen receptor modulators could be useful in complementary treatment.These observations could guide further somatic,as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.
文摘BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor pool.Safe utilization of these extended criteria grafts is paramount given the increased risk associated with their use in transplantation.Prognostic factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are lacking.AIM To understand the relationship between interleukin-33(IL-33)and complement in recipients immediately following liver reperfusion as a marker of liver dysfunction.METHODS Cohort consisted of patients who received a liver transplant from September 2016–September 2019 at our institution.Clinical variables were retrospectively extracted from the electronic medical record.Back-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a boardcertified pathologist.Blood samples were available immediately following liver transplantation.Quantification of plasma IL-33 and complement proteins,C3a and C5a,were determined by enzyme-linked immunosorbent assay.For mRNA expression,RNA was extracted from donor biopsies and used against a 780 gene panel.RESULTS Cohort consisted of 99 donor and recipients.Donor median age was 45 years and 55%male.Recipients had a median age of 59 years with 62%male.The main etiologies were alcoholic hepatitis,nonalcoholic steatohepatitis,and hepatocellular carcinoma.Median MELD-Na at transplant was 21.Donors were grouped based on moderate macrosteatosis(≥30%).Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase(P<0.001 and P<0.004),and increased incidence of early allograft dysfunction(60%compared to 18%).Circulating IL-33 levels were significantly elevated in recipients of≥30%macrosteatotic grafts(P<0.05).Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly higher alanine aminotransferase/aspartate aminotransferase(P<0.05 and P<0.01).Activated complement(C3a and C5a)were elevated in recipients implanted with moderate macrosteatotic grafts.RNA expression analysis of donor biopsies revealed moderate steatotic grafts upregulated genes inflammatory processes while downregulated hepatocyte-produced complement factors.CONCLUSION Circulating IL-33 and activated complement levels immediately following liver reperfusion in recipients of moderate macrosteatotic grafts may identify which patients are at risk of early allograft dysfunction.
基金National Natural Science Foundation of China(81801894,81760341)Basic Science and Frontier Technology Research Project of Chongqing Science and Technology Commission(cstc 2016jcyjA0005)+1 种基金Science and Technology Research Project of Chongqing Education Commission(KJ1702034)Traditional Chinese Medicine Science and Technology Project of Chongqing Health and Family Planning Commission(ZY201702071).
文摘Interleukin (IL) 33 is a key cytokine in type II immune and airway diseases. It is abundantly expressed in lung epithelial cells and plays an important role in both innate and adaptive immunity. In innate immunity, IL-33 responds promptly to produce an immune response that maintains homeostasis. In adaptive immunity, IL-33 interacts with various immune cells. At the same time, IL-33 also plays an important role in chronic inflammation of the airway and its remodeling. This article reviews the relevant biological knowledge of IL-33 and its research progress in lung immunity, and discusses the related issues of IL-33 as a lung immune test site and therapeutic target.
基金supported by the Fundamental Research Grant Scheme(FRGS)from the Malaysia Ministry of Higher Education(FRGS/1/2016/SKK10/UPM/02/1).
文摘Objective:To determine the involvement and the modulatory effects of IL-33 during Plasmodium berghei ANKA(PbA)infection.Methods:PbA infection in male ICR mice was utilized as a model of malaria.Systemically circulating IL-33 levels were determined in blood plasma by enzyme-linked immunosorbent assay(ELISA).After 24 hours post-inoculation of PbA,recombinant IL-33 and ST2,and antibodies against IL-33 and IgG treatments were administered daily for 3 days.Tissue expression and localization of IL-33 were assessed in organs generally affected by malaria via immunohistochemistry.Moreover,histopathological examination was performed to assess the effects of the treatments.Results:The levels of systemic IL-33 were elevated at the critical phase of PbA infection.Likewise,immunohistochemical analysis revealed a significant upregulation of IL-33 expression at the critical phase in the brain,lungs,and spleen of PbA-infected mice as compared to healthy controls.Treatment with IL-33 protected against experimental cerebral malaria development and reduced pathological features in the brain and lungs of the PbA-infected mice.Conclusions:A potential critical role and involvement of IL-33 in PbA infection may hint at the resolution of immunopathological sequelae associated with malaria.
基金Chongqing Municipal Health and Family Planning Commission Chinese Medicine Science and Technology Project(No.ZY201702071)Chongqing Municipal Health and Family Planning Commission Medical Research Project(No.2018MSXM097)。
文摘Objective:To investigate the effects of rhubarb enema on the expression of inflammatory factors and interleukin-33(IL-33)and its prognosis in patients with SAP complicated with sepsis.Methods:A total of 47 patients with SAP complicated with ARDS admitted to the Department of Critical Care Medicine,the First Affiliated Hospital of Chongqing Medical University from June 2016 to December 2018 were randomly divided into SAP with ARDS sepsis group(sepsis group)and SAP.In the ARDS non-sepsis group(non-sepsis group),20 patients were treated according to the guidelines for the diagnosis and treatment of acute pancreatitis in China in 2013.They were given regular fasting,gastrointestinal decompression,fluid resuscitation,acid suppression,and growth.On the basis of the inhibition of water,electrolytes,acid-base balance,add rhubarb 3 g/kg,water 200 mL,filter the slag juice to 37~38℃for retention enema for more than 15min,2 times a day For a total of 7 days.The inflammatory markers WBC,PCT,heart rate,respiratory rate,oxygenation index(PaO2/FiO2),pancreatic severity score(BISAP),and IL-33 and various cytokine changes were recorded in the two groups.Results:On the first day of admission,the patients in the sepsis group had more severe inflammation index(WBC:14.23±2.95,PCT:3.62±2.04,heart rate:104.02±8.89,respiration:26.81±2.44),and the oxygenation index was more.Poor(PaO2/FiO2:164.08±21.05),IL-33(46.32±7.82)and higher cytokine expression(TNF-α:266.78±72.89,IL-1:53.47±10.52,IL-6:1824.68±598.53,IL-8:160.42±50.34),the difference was statistically significant compared with the non-sepsis group,P<0.01.After the treatment of rhubarb enema,the above indicators were significantly decreased in both groups,and admission.The difference was statistically significant on the first day,P<0.01.However,on the seventh day after treatment,the sepsis patients hadΔIL-33(41.63±7.86)and cytokines(ΔTNF-α:258.90±72.18,ΔIL-1:47.87±11.85,ΔIL-6:1775.57±598.31,ΔIL-8:143.12±51.98),oxygenation index(162.01±43.23)improved better than non-sepsis group,P<0.01,and the rate of invasive ventilation was not statistically significant.P>0.05.Conclusion:SAP combined with sepsis leads to the use of rhubarb enema in patients with ARDS to significantly improve the concentration of IL-33 as a"target"factor and reduce the proinflammatory factors TNF-α,IL-1,IL-6 and IL-8.Level,improve the patient's oxygenation,has clinical application value.
基金Natural Science Foundation of China,No.81803069Zhejiang Medical Technology Plan Project,No.2019RC007,No.2019KY007 and No.2021KY047Funds of Science Technology Department of Zhejiang Province,No.LGF21H160033.
文摘Colorectal cancer(CRC)is presently the second most prevalent global mortalityinducing cancer.CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment.In addition,non-neoplastic cell activities within tumor microenvironments for CRC development have been established.However,interleukin(IL)-33,secreted by such cell types,plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment.IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity(ST)2 receptor.Therefore,how to coordinate tumor microenvironment,design and optimize treatment strategies suitable for CRC,based on IL-33/ST2 signal is a challenge.Even though it has established influences upon immunitylinked conditions,IL-33 effects on CRC progression and prevention and related mechanisms are still controversial.Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention.Moreover,IL-33/ST2 signaling is a potential therapeutic target for CRC.
基金supported by the National Natural Science Foundation of China(82271401,82071394)the Tianjin Health Research Project(TJWJ2024RC002)。
文摘Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.
文摘目的:分析白细胞介素-33(interleukin-33,IL-33)在不同程度支气管哮喘患者中的变化及其与气道重塑的剂量-反应关系。方法:回顾性分析2022年5月至2024年5月于本院接受治疗的150例支气管哮喘患者的临床资料,根据疾病程度将所有患者分为重度组(81例)、中度组(46例)和轻度组(23例)。根据气道面积/总横截面积比值(airway area to total cross-sectional area ratio,WA)将所有患者分为气道重塑组(WA≥60%,57例)和非气道重塑组(WA<60%,93例)。比较不同疾病程度支气管哮喘患者的临床资料及IL-33变化。分析IL-33水平与支气管哮喘患者气道重塑指标的相关性。广义可加模型分析疾病程度与相关因素的关系。采用多因素logistic回归分析确定支气管哮喘患者气道重塑的独立风险预测因子。通过限制性立方样条模型评估IL-33水平与气道重塑的剂量-反应关系。采用受试工作者特征曲线分析IL-33水平对气道重塑的预测价值。结果:重度哮喘患者的IL-33、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)水平明显升高,金属蛋白抑制剂-1(tissue inhibitor of metalloprotein inhibitors-1,TIMP-1)水平明显降低(P<0.05)。IL-33水平MMP-9、TGF-β1呈正相关,与TIMP-1呈负相关(P<0.05)。多因素logistic回归分析结果显示,呼吸道感染、吸烟、嗜酸性粒细胞计数>1.55%、TIMP-1≤112.09µg/L、MMP-9>7.34 ng/mL、TGF-β1>3.77 ng/mL、白细胞介素-17>16.03 ng/L、IL-33>790.02 ng/L、重度哮喘均为影响支气管哮喘患者气道重塑的独立危险因素(P<0.05)。限制性立方样条模型结果显示,IL-33水平与气道重塑的关联强度呈非线性剂量反应关系(P<0.05)。IL-33水平对气道重塑具有一定的预测价值(曲线下面积=0.767)。结论:重度哮喘患者的IL-33水平明显升高,且IL-33水平是支气管哮喘患者气道重塑的重要影响因素,与患者气道重塑呈非线性剂量-反应关系。
