Journal
CELLULAR IMMUNOLOGY
Volume 201, Issue 2, Pages 77-82Publisher
ACADEMIC PRESS INC
DOI: 10.1006/cimm.2000.1650
Keywords
TNF; PPAR-gamma; NF-kappa B; Jurkat cells; apoptosis
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Funding
- NIAID NIH HHS [AI41060] Funding Source: Medline
- NIAMS NIH HHS [AR44914] Funding Source: Medline
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The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the TNF family. Unlike many other members of the TNF family, TRAIL selectively induces apoptosis of tumor cells, but not normal cells. The mechanisms whereby TRAIL-induced apoptosis is regulated in various cell types are not clear. We report here that the peroxisome proliferator-activated receptor (PPAR)-gamma and nuclear factor (NF)-kappa B play distinct roles in regulating TRAIL-induced apoptosis. Activation of PPAR-gamma by its agonist pioglitazone significantly enhanced TRAIL-induced apoptosis, This was associated with inhibition of proliferation and cell cycle progression. On the other hand, inhibition of NF-kappa B by sulfasalazine also significantly enhanced TRAIL-induced apoptosis, These results strongly suggest that while transcription factor PPAR-gamma promotes TRAIL-induced apoptosis, NF-kappa B inhibits it. Thus, PPAR-gamma agonists and NF-kappa B inhibitors are potent enhancers of TRAIL-induced apoptosis. (C) 2000 Academic Press.
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