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.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Alikhani M,Alikhani Z,Raptis M,Graves DTdoi
10.1002/jcp.20067keywords:
subject
Has Abstractpub_date
2004-12-01 00:00:00pages
341-8issue
3eissn
0021-9541issn
1097-4652journal_volume
201pub_type
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