STAT1及STAT3在Con A引起肝炎反應所扮演的角色研究
The role of STAT1 or STAT3 in Con A-induced hepatitis
Date Issued
2004
Date
2004
Author(s)
Kuan, Lo
DOI
en-US
Abstract
Concanavalin A (Con A)-induced severe liver damage in mice is considered a model for human hepatitis. Although this model has been established for decades, the underlying mechanisms are still not fully understood. By using STAT1 traditional knockout mice and conditional knockout mice lacking STAT3 in the liver, the roles of STAT1 and STAT3, two important transcriptional factors, in Con A-induced hepatitis are investigated.
Both STAT1 and STAT3 are transiently activated in the hepatocytes of wild-type (WT) mice by tyrosine phosphorylation following Con A administration. While levels of STAT3 activation in STAT1 knockout (ST1KO) mice are comparable to that of Wild-type (WT) mice, STAT1 activation, however, is enhanced in STAT3 conditional knockout (ST3KO) mice. Interestingly, Con A-induced hepatitis is greatly impaired in mice either lacking STAT1 or STAT3 in the liver, with reduced serum alanine transaminase (ALT) and asparate transaminase (AST), less severe liver damage in histological sections, and decreased caspase-3 activity in the Con A-treated hepatocytes.
The mechanisms of mutant mice resistant to Con A-induced hepatitis are further explored. First of all, the number of intrahepatic leukocytes (IHLs), including natural killer T (NKT), CD4+ T cells, and granulocytes are found to be similar between WT and ST3KO mice before and after Con A treatment, suggesting that the recruitment of these effector cells to liver is normal in the absence of STAT3. Secondly, profiles of serum pro-inflammatory cytokines such as IFN-
Subjects
肝炎模式
訊息傳遞
發炎
肝臟
SOCS1
NKT
IHL
STAT3
STAT1
ALT
Con A-induced hepatitis
SOCS3
AST
SDGs
Type
other
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