Rifampicin Inhibits CD95-mediated Apoptosis of Jurkat T Cells Via Glucocorticoid Receptors by Modifying the Expression of Molecules Regulating Apoptosis

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2002 Apr 18

PMID 11958592

Citations 4

Authors

Rama Yerramasetti

Sastry Gollapudi

Sudhir Gupta

Affiliations

Soon will be listed here.

Abstract

Rifampicin and its analogues are increasingly used in the treatment and prophylaxis of mycobacterial infections. Recently, it has been demonstrated that rifampicin binds to and activates glucocorticoid receptors (GR). Glucocorticoids may inhibit or promote apoptosis in various cell types. Therefore, we investigated the effect of rifampicin on anti-CD95-induced apoptosis in Jurkat T cells. Rifampicin, in a concentration-dependent manner, inhibited anti-CD95-induced apoptosis. Furthermore, rifampicin down-regulated the expression of Bax and CD95L and up-regulated the expression of Bcl-2, Bcl-xL, and Flice-inhibitory protein-L (FLIPL); however, rifampicin had no effect on CD95 or XIAP expression. Rifampicin did not inhibit the binding of anti-CD95 monoclonal antibody to CD95 receptor. A GR-specific antagonist RU480 reversed the inhibition of apoptosis by rifampicin. Furthermore, rifampicin failed to inhibit anti-CD95-induced apoptosis in a dominant negative IKBalpha (IKBaM) Jurkat T cells. Taken together, these findings suggest that rifampicin inhibits anti-CD95-induced apoptosis in Jurkat T cells by modulating the expression of various molecules regulating apoptosis and its effect appears to be mediated via GR and at least in part through NF-kappaB signaling pathway.

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