Prostaglandin E-2 inhibits T cell activation-induced apoptosis and Fas-mediated cellular cytotoxicity by blockade of Fas-ligand induction

Prostanoids exhibit both pro-apoptotic and anti-apoptotic functions dependi ng on the maturation stage and tissue localization of target cells. Prostag landin (PG) E-2 has been shown to protect T lymphocytes from TCR-mediated a ctivation-induced cell death, but the mechanism by which PGE(2) inhibits ap optosis of T cells has not been established. We show that this protection i nvolves the down-regulation of Fas-ligand (Fas-L) mRNA levels in T cells. M odulation of cell surface Fas-L expressin by physiological concentrations o f PGE(2) was shown to be both anti-apoptotic as well as capable of inhibiti ng Fas-L-mediated cytotoxicity of Fas-transfected P815 target cells. Thus, this study provides direct evidence of the likely biological means by which PGE(2) down-regulates T cell apoptosis.