Thiols prevent Fas (CD95)-mediated T cell apoptosis by down-regulating membrane Fas expression.
Thiol antioxidants have been shown to protect cells against apoptosis. Based on the role of Fas in T cell apoptosis, we investigated the effect of thiols on Fas expression. We report that the thiol N-acetyl-L-cysteine (NAC) prevents the induction of Fas on human peripheral blood T cells in a dose-dependent manner. It also down-regulates in a time- and dose-dependent manner Fas expression on Fas-expressing T cells. Although these effects were not mediated through de novo glutathione synthesis, only compounds with a free thiol group decreased membrane Fas expression. The decrease of Fas expression induced by NAC was not associated with a modulation of Fas mRNA transcription nor with an internalization, suggesting that NAC may affect the processing of Fas. Indeed, a soluble immunoreactive form of Fas was detected by ELISA and by Western blotting in the supernatants of Fas-expressing T cells treated with NAC. As a functional consequence, NAC partly protected Jurkat cells against Fas-mediated apoptotic cell death. Thus, this study shows that, by regulating Fas expression, the cytoprotective properties of NAC can be extended to Fas-mediated cell death.
Delneste
Y
Y
Immunology Department, Geneva Biomedical Research Institute, Switzerland.
Jeannin
P
P
Sebille
E
E
Aubry
J P
JP
Bonnefoy
J Y
JY
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects*; D019014:fas Receptor / Q000096:biosynthesis* / Q000187:drug effects*
D000975:Antioxidants; D008565:Membrane Proteins; D019014:fas Receptor; D000111:Acetylcysteine