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
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
Objective： Allergic airway diseases （AADs） are a group of heterogeneous disease mediated by T-helper type 2 （Th2） immune response and characterized with airway inflammation and remodeling, including allergic asth...Objective： Allergic airway diseases （AADs） are a group of heterogeneous disease mediated by T-helper type 2 （Th2） immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. Data Sources： Articles referred in this review were collected from the database of PubMed published in English up to January 2018. Study Selection： We had done a literature search using the following terms ＂allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte＂. Related original or review articles were included and carefully analyzed. Results： It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin （IL）-25, IL-33, and thymic stromal lymphopoietin （TSLP）, are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. Conclusions： In view of the redundancy ofcytokines and ＂united airway＂ theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.展开更多
Background Interleukin （IL）-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/r...Background Interleukin （IL）-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion （I/R） injury. Methods Male BALB/c mice （（22＋3） g） were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups： control group （laparotomy only, without blocking blood supply） and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups： control, model （injection of rabbit IgG polyclonal antibody）, recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, IL-4, IL-5, IL-13, interferon-y （IFN-y） and tumor necrosis factor-a （TNF-a） levels were measured. Results Levels of IL-33 mRNA and protein did not change during ischemia （P 〉0.05） but increased significantly during reperfusion （P 〈0.05）. After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-~ and TNF-a were significantly increased （P 〈0.05）, and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-y decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-r levels compared with controls （P 〈0.05）. There was no change in the level of TNF-a. Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Thl to Th2 shift.展开更多
Interleukin-33(IL-33)is the most attractive novel cytokine identified as an IL-1 family member.IL-33 was first named NF-HEV(nuclear factor from high endothelial venules),as it was known to interact with nuclear chroma...Interleukin-33(IL-33)is the most attractive novel cytokine identified as an IL-1 family member.IL-33 was first named NF-HEV(nuclear factor from high endothelial venules),as it was known to interact with nuclear chromatin although its exact intracellular functions are still to be clarified.IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor family member ST2 and to be involved in polarization of T cells towards T helper 2 cell phenotype and in activation of mast cells,bosophils,eosinophils and natural killer cells.It is essential for IL-33 to be extracellularly released in order to bind to the ST2 receptor and consequently play a crucial role in inflammatory,infectious and autoimmune diseases.However,like the IL-1 family members,IL-1b and IL-18,IL-33 mRNA is translated without a signal sequence for secretion.Additionally,IL-33 cannot be released by the processing and secretion mechanism shared by IL-1b and IL-18 as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation.In contrast,IL-33 can be inactivated by apoptotic caspases.Accordingly,IL-33 is proposed to be released as an alarmin from necrotic cells but to be deleted during apoptosis.Besides the known autocrine,paracrine,intracrine,juxtacrine and retrocrine mechanisms of cellular interaction with cytokines,release by necrotic cells is another pathway for a cytokine to display its function,which we suggest might be called‘necrocrine’.This mini review summarizes recent progress of how IL-33 displays potential immunoregulatory roles with a particular focus on its enigmatic production.展开更多
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(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This study was supported by grants from the Natural Science Foundation of China （No. 81641003） and Application of Clinical Features in Capital City by the Beijing Municipal Science and Technology Commission （No. Z131107002213135）.
文摘Objective： Allergic airway diseases （AADs） are a group of heterogeneous disease mediated by T-helper type 2 （Th2） immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. Data Sources： Articles referred in this review were collected from the database of PubMed published in English up to January 2018. Study Selection： We had done a literature search using the following terms ＂allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte＂. Related original or review articles were included and carefully analyzed. Results： It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin （IL）-25, IL-33, and thymic stromal lymphopoietin （TSLP）, are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. Conclusions： In view of the redundancy ofcytokines and ＂united airway＂ theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.
文摘Background Interleukin （IL）-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion （I/R） injury. Methods Male BALB/c mice （（22＋3） g） were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups： control group （laparotomy only, without blocking blood supply） and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups： control, model （injection of rabbit IgG polyclonal antibody）, recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, IL-4, IL-5, IL-13, interferon-y （IFN-y） and tumor necrosis factor-a （TNF-a） levels were measured. Results Levels of IL-33 mRNA and protein did not change during ischemia （P 〉0.05） but increased significantly during reperfusion （P 〈0.05）. After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-~ and TNF-a were significantly increased （P 〈0.05）, and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-y decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-r levels compared with controls （P 〈0.05）. There was no change in the level of TNF-a. Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Thl to Th2 shift.
文摘Interleukin-33(IL-33)is the most attractive novel cytokine identified as an IL-1 family member.IL-33 was first named NF-HEV(nuclear factor from high endothelial venules),as it was known to interact with nuclear chromatin although its exact intracellular functions are still to be clarified.IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor family member ST2 and to be involved in polarization of T cells towards T helper 2 cell phenotype and in activation of mast cells,bosophils,eosinophils and natural killer cells.It is essential for IL-33 to be extracellularly released in order to bind to the ST2 receptor and consequently play a crucial role in inflammatory,infectious and autoimmune diseases.However,like the IL-1 family members,IL-1b and IL-18,IL-33 mRNA is translated without a signal sequence for secretion.Additionally,IL-33 cannot be released by the processing and secretion mechanism shared by IL-1b and IL-18 as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation.In contrast,IL-33 can be inactivated by apoptotic caspases.Accordingly,IL-33 is proposed to be released as an alarmin from necrotic cells but to be deleted during apoptosis.Besides the known autocrine,paracrine,intracrine,juxtacrine and retrocrine mechanisms of cellular interaction with cytokines,release by necrotic cells is another pathway for a cytokine to display its function,which we suggest might be called‘necrocrine’.This mini review summarizes recent progress of how IL-33 displays potential immunoregulatory roles with a particular focus on its enigmatic production.
