| First Author | Tsai CC | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 7 | Pages | 3867-77 |
| PubMed ID | 21873526 | Mgi Jnum | J:179336 |
| Mgi Id | MGI:5301795 | Doi | 10.4049/jimmunol.1100770 |
| Citation | Tsai CC, et al. (2011) Glycogen synthase kinase-3 facilitates con a-induced IFN-gamma-- mediated immune hepatic injury. J Immunol 187(7):3867-77 |
| abstractText | Immune hepatic injury induced by Con A results primarily from IFN-gamma-mediated inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3, which acts proapoptotically and is proinflammatory, is also important for facilitating IFN-gamma signaling. We hypothesized a pathogenic role for GSK-3 in Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of C57BL/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes, and deregulated expression of adhesion molecule CD54. Con A induced hepatic injury in an IFN-gamma receptor 1-dependent manner. Con A/IFN-gamma induced activation and expression of STAT1 in a GSK-3-dependent manner. GSK-3 facilitated IFN-gamma-induced inducible NO synthase, but had limited effects on CD95 upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting GSK-3 decreased Con A-induced IFN-gamma production in both wild-type and IFN-gamma receptor 1-deficient C57BL/6 mice. In Con A-activated NKT cells, GSK-3 was also activated and was required for nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-gamma, but it was not required for CD95 ligand expression or activation-induced cell death. These results demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by facilitating IFN-gamma-induced hepatopathy. |
