• Home
  • Search Results
  • STAT4 knockout mice are more susceptible to concanavalin A-induced T-cell hepatitis.

STAT4 knockout mice are more susceptible to concanavalin A-induced T-cell hepatitis.

The American journal of pathology (2014-04-16)
Yan Wang, Dechun Feng, Hua Wang, Ming-Jiang Xu, Ogyi Park, Yongmei Li, Bin Gao
ABSTRACT

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 Il12a(-/-) and Il12b(-/-) 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 Il12b 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
SAFC
BIS-TRIS
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
BIS-TRIS, BioPerformance Certified, suitable for cell culture, suitable for insect cell culture, ≥98.0%
SAFC
BIS-TRIS
Sigma-Aldrich
Monoclonal Anti-CD3 antibody produced in mouse, clone OKT3, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-CD3, low endotoxin antibody, Mouse monoclonal, clone OKT3, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-CD3E antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal Anti-CD95 antibody produced in mouse, clone LT95, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD3 antibody produced in mouse, clone MEM-57, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD3 antibody produced in mouse, clone MEM-92, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD3 antibody produced in mouse, clone APA1/1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-FAS antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Glutathione Reductase antibody, Mouse monoclonal, clone GR6, purified from hybridoma cell culture
Sigma-Aldrich
Anti-FAS antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-FAS (ab1) antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-FAS (ab2) antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD3E antibody produced in mouse, clone 4C1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-FAS antibody produced in mouse, clone 2G3, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-GSR antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Monoclonal Anti-CD3 antibody produced in mouse, clone UCHT-1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD3E antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1466, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Monoclonal Anti-CD3E antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1497, purified immunoglobulin, buffered aqueous glycerol solution