TNF-alpha in vivo stimulates apoptosis in fibroblasts through caspase-8 activation and modulates the expression of pro-apoptotic genes

Citation:

M. Alikhani, Z. Alikhani, M. Raptis, and D. T. Graves. 2004. “TNF-alpha in vivo stimulates apoptosis in fibroblasts through caspase-8 activation and modulates the expression of pro-apoptotic genes.” J Cell PhysiolJ Cell PhysiolJ Cell Physiol, 201: 341-8.

Abstract:

Apoptosis of matrix producing cells is common among many inflammatory diseases. The goal of the present study was to examine the apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) on fibroblastic cells in vivo and to investigate the role of different caspases in this process. This was accomplished in vivo by subcutaneous injection of TNF-alpha in mice. The direct effects of TNF-alpha on fibroblast apoptosis were studied in vitro with normal diploid human fibroblasts. The results indicate that TNF-alpha in vivo induces apoptosis of fibroblasts. By RNase protection assay, we demonstrated that TNF-alpha stimulates expression of 12 apoptotic genes. Fluorometric studies demonstrated that TNF-alpha in vivo predominantly increased caspase-8 and -3 activity and by use of specific inhibitors, the activation of caspase-3 was shown to be initiated by caspase-8 with only a minor contribution from caspase-9. Thus, TNF-alpha acts to modulate the expression of many genes that favors apoptosis of fibroblastic cells, which is dependent mostly upon signaling through caspase-8.

Notes:

Alikhani, ManiAlikhani, ZoubinRaptis, MarkosGraves, Dana TDE07559/DE/NIDCR NIH HHS/United StatesDE11254/DE/NIDCR NIH HHS/United StatesJournal ArticleResearch Support, U.S. Gov't, P.H.S.United StatesJ Cell Physiol. 2004 Dec;201(3):341-8.