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学科主题: 临床医学
题名:
STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced T-Cell Hepatitis
作者: Wang, Yan1,2; Feng, Dechun1; Wang, Hua1; Xu, Ming-Jiang1; Park, Ogyi1; Li, Yongmei1; Gao, Bin1
刊名: AMERICAN JOURNAL OF PATHOLOGY
发表日期: 2014-06-01
DOI: 10.1016/j.ajpath.2014.02.023
卷: 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
所属项目编号: 81300312 ; N01-DK-7-0004/HHSN267200700004C
项目资助者: NIH-National Institute on Alcohol Abuse and Alcoholism ; China Scholarship Council ; Wu Mengchao Medical Science Foundation ; National Natural Science Foundation of China ; NIH
WOS记录号: WOS:000336948700016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55290
Appears in Collections:北京大学第一临床医学院_感染疾病科_期刊论文

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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

Recommended Citation:
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.
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