Endogenous prostaglandins E2 and F2α serve as an anti-apoptotic factor against apoptosis induced by tumor necrosis factor-α in mouse 3T3-L1 preadipocytes

Adipocytes can function as endocrine cells secreting a variety of adipocytokines including tumor necrosis factor (TNF)-alpha. Treatment of cultured mouse 3T3-L1 preadipocytes with TNF-alpha induced apoptosis, as was evident from increases in nuclear condensation and caspase-3 activity, but differentiated adipocytes during the maturation phase showed resistance to apoptosis by TNF-a. Antioxidants effectively reduced TNF-alpha-induced apoptosis in preadipocytes, indicating the involvement of reactive oxygen species. Exposure of preadipocytes to calcium ionophore A23187 reduced TNF-alpha-induced apoptosis, which was accompanied by increased production of prostaglandins (PGs) E-2 and PGF(2 alpha). TNF-alpha preferentially promoted gene expression of cyclooxygenase (COX)-2 without affecting that of COX-1. Consistently, NS-398, a COX-2 inhibitor, stimulated TNF-alpha-induced apoptosis, which was reversed by exogenous PGE(2) and PGF(2 alpha). These results indicate that endogenous PGE(2) and PGF(2 alpha) synthesized by preadipocytes through the induction of COX-2 can serve as antiapoptotic factors against apoptosis by TNF-alpha.