LPS-induced Apoptosis is Partially Mediated by Hydrogen Sulphide in RAW 264.7 Murine Macrophages.

Lipopolysaccharide (LPS) induces apoptosis in murine macrophages through the autocrine secretion of tumor necrosis factor (TNF)-α and nitric oxide (NO). LPS-induced inflammation in murine macrophages is associated with hydrogen sulfide (HS) production. In this present study, we reported the novel role of HS in LPS-induced apoptosis and its underlying molecular mechanism specifically at late phases in murine macrophage cells. Stimulation of RAW 264.7 macrophages with LPS resulted in a time- and dose-dependent induction of apoptosis. We observed that the LPS-induced early apoptosis (associated with TNF-α secretion) in macrophages was not inhibited in the presence of HS inhibitor (DL-propargylglycine), whereas early apoptosis was absent in the presence of TNF receptor antibody. Interestingly, LPS-induced late apoptosis paralleled with HS production was reduced in the presence of HS inhibitor but not with TNF receptor antibody. The late apoptotic events mediated by HS and not the TNF-α induced early apoptosis correlated significantly with the induction of p53 and Bax expression in LPS-induced macrophages. Thus, it is possible that RAW 264.7 murine macrophages treated with LPS mediated early apoptosis through TNF-α and the late apoptotic events through the production of HS.