Thiols prevent Fas (CD95)-mediated T cell apoptosis by down-regulating membrane Fas expression

✍ Scribed by Yves Delneste; Pascale Jeannin; Eric Sebille; Jean-Pierre Aubry; Jean-Yves Bonnefoy

• Book ID: 102827383
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 748 KB
• Volume: 26
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830261225

✦ Synopsis

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.