LPS induces direct death of IFN-γ primed murine embryonic hepatocyte, BNL CL2 cells in a TNF-α independent manner

Although it has been well known that the role of LPS on liver damage is mediated through TNF-α, the mechanism by which LPS modulates the cytotoxicity of IFN-γ on hepatocytes has not yet been clearly demonstrated. Here, we demonstrate that IFN-γ mediated apoptosis in murine embryonic hepatocyte BNL CL2 cells is potentiated by the addition of LPS (0.5 μg/ml). Consistently, LPS markedly increases the catalytic activity of caspase 3-like protease but not caspase 1-like protease in IFN-γ treated cells. In addition, TNF-α alone does not affect cell viability but rather it potentiates the cytotoxic effect of IFN-γ on BNL CL2 cells. However, the cell viability of IFN-γ/LPS treated cells is affected by the addition of polymyxin B but not by TNF binding protein I (TNF-BPI). These data suggest that the lipid moiety of LPS may mediate direct cytotoxicity of BNL CL2 cells in a TNF-α independent manner.