Prostaglandin E2 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 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 expression 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.
Porter
B O
BO
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA.
Malek
T R
TR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D053222:Fas Ligand Protein; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D015232:Dinoprostone