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-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
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
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
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(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.
