Prostaglandin E2 inhibits T cell activation-induced apoptosis and Fas-mediated cellular cytotoxicity by blockade of Fas-ligand induction

Abstract

Prostanoids exhibit both pro-apoptotic and anti-apoptotic functions depending on the maturation stage and tissue localization of target cells. Prostaglandin (PG) E₂ has been shown to protect T lymphocytes from TCR-mediated activation-induced cell death, but the mechanism by which PGE₂ inhibits apoptosis of T cells has not been established. We show that this protection involves the down-regulation of Fas-ligand (Fas-L) mRNA levels in T cells. Modulation of cell surface Fas-L expressin by physiological concentrations of PGE₂ was shown to be both anti-apoptotic as well as capable of inhibiting Fas-L-mediated cytotoxicity of Fas-transfected P815 target cells. Thus, this study provides direct evidence of the likely biological means by which PGE₂ down-regulates T cell apoptosis.