Molecular basis of rifampicin-induced inhibition of anti-CD95-induced apoptosis of peripheral blood T lymphocytes: the role of CD95 ligand and FLIPs.
Rifampicin modulates immune response; however, mechanisms by which it exerts these effects are incompletely understood. Recently, rifampicin has been shown to bind to and activate glucocorticoid receptors. Because of the evidence for a role of glucocorticoids in lymphocyte apoptosis, we hypothesized that rifampicin may exert its influence on the immune system by regulating apoptosis. Therefore, we examined the effect of rifampicin on signaling pathway of anti-CD95-induced apoptosis in peripheral blood lymphocytes. Rifampicin, in a concentration-dependent manner, inhibited anti-CD95-induced apoptosis in both CD4+ and CD8+ T cells, which was associated with the inhibition of activation of both caspase-3 and caspase-8. In addition, rifampicin down-regulated the expression of CD95L and Bax. The inhibitory effects of rifampicin on apoptosis and caspase activation as well as its effect on the expression of CD95L and FLIPs were reversed by RU486, an antagonist of glucocorticoid receptor. These data suggest that rifampicin inhibits anti-CD95-mediated apoptosis in lymphocytes by modulating the expression of certain proteins that regulate apoptosis, at least in part, via glucocorticoid receptors.
Gollapudi
Sastry
S
Laboratory of Cellular Immunology, Division of Basic and Clinical Immunology, University of California, Irvine, California 92697, USA. sgollap@uci.edu
Jaidka
Suman
S
Gupta
Sudhir
S
D000328:Adult; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology*
D000904:Antibiotics, Antitubercular; D000906:Antibodies; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006727:Hormone Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019014:fas Receptor; D015735:Mifepristone; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D012293:Rifampin