Butyric acid-induced T-cell apoptosis is mediated by caspase-8 and-9 activation in a Fas-independent manner

Our previous study demonstrated that butyric acid, an extracellular metabol ite of periodontopathic bacteria, induced apoptosis in murine thymocytes, s plenic T cells, and human Jurkat cells, In this study, we examined whether CD95 ligand-receptor interaction is involved in butyric acid-induced T-cell apoptosis, Flow cytometry analysis indicated that expression of Fas in Jur kat and T cells from peripheral blood mononuclear cells was not affected by butyric acid treatment, Furthermore, the expression of Fas and FasL protei n in Western blotting was not affected by butyric acid treatment. Coincubat ion with blocking anti-Fas antibodies prevented Fas-induced apoptosis but n ot butyric acid-induced apoptosis, Anti-Fast antibodies also did not preven t butyric acid-induced apoptosis at any dose examined. Although cytotoxic a nti-Fas antibody affected butyric acid-induced apoptosis, a synergistic eff ect was not seen. Time-dependent activation of caspase-8 and -9 was recogni zed in butyric acid- as well as Fas-mediated apoptosis, IETD-CHO and LEHD-C HO, specific inhibitors of caspase8 and -9, respectively completely blocked Fas-mediated apoptosis and partially prevented butyric acid induced apopto sis, These results suggest that the Fas-FasL interaction is not involved in butyric acid-induced apoptosis and that caspase-8 and -9-dependent apoptos is plays an important role in butyric acid-induced apoptosis, as well as Fa s-induced apoptosis.