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STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced T-Cell Hepatitis
Wang, Yan1,2; Feng, Dechun1; Wang, Hua1; Xu, Ming-Jiang1; Park, Ogyi1; Li, Yongmei1; Gao, Bin1
刊名AMERICAN JOURNAL OF PATHOLOGY
2014-06-01
DOI10.1016/j.ajpath.2014.02.023
184期:6页:1785-1794
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pathology
研究领域[WOS]Pathology
关键词[WOS]GENOME-WIDE ASSOCIATION ; MEDIATED LIVER-INJURY ; ISCHEMIA/REPERFUSION INJURY ; SERINE PHOSPHORYLATION ; IFN-GAMMA ; IL-12 ; INFLAMMATION ; ACTIVATION ; INTERLEUKIN-12 ; INVOLVEMENT
英文摘要

STAT4, which is activated mainly by IL-12, promotes inflammatory responses by inducing Th1 and Th2 cytokines. Recent genome-wide association studies indicate that STAT4 gene variants are associated with risk of various types of liver diseases, but how STAT4 contributes to liver disease pathogenesis remains obscure. In this study, STAT4 activation was detected in liver immune cells from patients with viral hepatitis and autoimmune hepatitis, as well as in a mouse model of concanavaLin A (Con A)-induced hepatitis. Such STAT4 activation was detected mainly in T cells, natural killer T cells, and macrophages and Kupffer cells, and was diminished in I112a/and 11/26/mice. As expected, disruption of the Stat4 gene reduced production of Th1 and Th2 cytokines, but surprisingly exacerbated Con A-induced liver injury. Similarly, disruption of IL12a or 11126 also augmented Con A-induced hepatocellular damage. Further studies showed that hepatic natural killer T (NKT) cells from Con A-treated Stat4(-/-) mice had higher levels of FasL expression and increased cytotoxicity against hepatocytes than those from Con A-treated WT mice. In vitro, blocking FasL attenuated Stat4(-/-) NKT cytotoxicity against hepatocytes. In conclusion, despite up-regulation of proinflammatory cytokines, STAT4 protects against acute T-cell hepatitis, which is mediated by direct or indirect down-regulation of FasL expression on NKT cells.

语种英语
WOS记录号WOS:000336948700016
项目编号81300312 ; N01-DK-7-0004/HHSN267200700004C
资助机构NIH-National Institute on Alcohol Abuse and Alcoholism ; China Scholarship Council ; Wu Mengchao Medical Science Foundation ; National Natural Science Foundation of China ; NIH
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55290
专题北京大学第一临床医学院_感染疾病科
作者单位1.NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA
2.Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Wang, Yan,Feng, Dechun,Wang, Hua,et al. STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced T-Cell Hepatitis[J]. AMERICAN JOURNAL OF PATHOLOGY,2014,184(6):1785-1794.
APA Wang, Yan.,Feng, Dechun.,Wang, Hua.,Xu, Ming-Jiang.,Park, Ogyi.,...&Gao, Bin.(2014).STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced T-Cell Hepatitis.AMERICAN JOURNAL OF PATHOLOGY,184(6),1785-1794.
MLA Wang, Yan,et al."STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced T-Cell Hepatitis".AMERICAN JOURNAL OF PATHOLOGY 184.6(2014):1785-1794.
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