Background Acute myocardial infarction （AMI） is a common cardiac emergency with high mortality.Serum soluble ST2 （sST2） is a new emerging biomarker of cardiac diseases.The present study is to investigate the predi...Background Acute myocardial infarction （AMI） is a common cardiac emergency with high mortality.Serum soluble ST2 （sST2） is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 （IL-33） for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph （ECG）,biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects （patients within 24 hours after acute attack） were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay （ELISA） kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different （P〈0.001）.In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course （〈24 hours） of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognos展开更多
Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we i...Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in mice.We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis.Liver injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient mice.Recombinant IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling.Finally,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis.In conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis.展开更多
Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33(IL-33) is a recently desc...Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33(IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage, IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models, with its actions strongly shaped by the local microenvironment. Recent studies have established a role for the IL-33-ST2 axis in the initiation and perpetuation of inflammation during endotoxemia, but its roles in sepsis appear to be organism and model dependent. In this review, we focus on the recent advances in understanding the role of the IL-33/ST2 axis in sepsis.展开更多
The iso fl avone calycosin-7-O-β-D-glucopyranoside(CG) is a principal constituent of Astragalus membranaceus(AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this...The iso fl avone calycosin-7-O-β-D-glucopyranoside(CG) is a principal constituent of Astragalus membranaceus(AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin(Ocal) m RNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2(BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family(WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.展开更多
文摘Background Acute myocardial infarction （AMI） is a common cardiac emergency with high mortality.Serum soluble ST2 （sST2） is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 （IL-33） for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph （ECG）,biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects （patients within 24 hours after acute attack） were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay （ELISA） kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different （P〈0.001）.In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course （〈24 hours） of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognos
基金This work was supported by grants from the National Natural Science Foundation(81502036 to ZT,81201595 to SS,81201528 to RJ)the Natural Science Foundation of Jiangsu Province(BK20151031 to ZT)+3 种基金the National Key Research and Development Program of China(2016YFC0905900 to BS)the State Key Program of National Natural Science of China(81430062 to BS)the project of the Nanjing Science and Technology Development Plan(201303033 to LL)The work was also supported in part by the Program for Development of Innovative Research Teams in the First Affiliated Hospital of NJMU,the Priority Academic Program of Jiangsu Higher Education Institutions and funds from CNRS and FEDER(BR).
文摘Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in mice.We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis.Liver injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient mice.Recombinant IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling.Finally,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis.In conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis.
基金supported by the National Institutes of Health(RO1-GM 044100,RO1-GM 050441)
文摘Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33(IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage, IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models, with its actions strongly shaped by the local microenvironment. Recent studies have established a role for the IL-33-ST2 axis in the initiation and perpetuation of inflammation during endotoxemia, but its roles in sepsis appear to be organism and model dependent. In this review, we focus on the recent advances in understanding the role of the IL-33/ST2 axis in sepsis.
基金supported by the National Natural Science Foundation of China, China (No. 31400304)the Natural Science Foundation of Hubei Province, China (No. 2012FFB00303)+1 种基金the Youth & Middle-aged Talent Project of Hubei Province (No. Q20111005)the Science and Technology Program of Shandong Province (No. J12LL07)
文摘The iso fl avone calycosin-7-O-β-D-glucopyranoside(CG) is a principal constituent of Astragalus membranaceus(AR) and has been reported to inhibit osteoclast development in vitro and bone loss in vivo. The aim of this study was to investigate the osteogenic effects of CG and its underlying mechanism in ST2 cells. The results show that exposure of cells to CG in osteogenic differentiation medium increases ALP activity, osteocalcin(Ocal) m RNA expression and the osteoblastic mineralization process. Mechanistically, CG treatment increased the expression of bone morphogenetic protein 2(BMP-2), p-Smad 1/5/8, β-catenin and Runx2, all of which are regulators of the BMP- or wingless-type MMTV integration site family(WNT)/β-catenin-signaling pathways. Moreover, the osteogenic effects of CG were inhibited by Noggin and DKK-1 which are classical inhibitors of the BMP and WNT/β-catenin-signaling pathways, respectively. Taken together, the results indicate that CG promotes the osteoblastic differentiation of ST2 cells through regulating the BMP/WNT signaling pathways. On this basis, CG may be a useful lead compound for improving the treatment of bone-decreasing diseases and enhancing bone regeneration.
