Effect of TNF-alpha on the induction of apoptosis in murine macrophages: role of interleukin-1 beta converting enzyme

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces apoptosis in various cell types via its binding to TNF-receptors (TNF-R). Involvement of ICE-like protease in the induction of TNF-alpha mediated apoptosis in murine macrophage was investigated using ICE inhibitor YVAD-cmk (Tetrapeptide-Acetyl-Try-Val Ala-Asp-Chloromethyl ketone). Macrophages treated with TNF showed a time dependent decrease in cell viability with a simultaneous increase in the percent of cells showing apoptotic morphology and an increase in percent DNA fragmentation, a quantitative measure of apoptosis. However, incubation of macrophage in medium containing TNF and YVAD-cmk had inhibitory effect on the TNF-induced apoptosis of macrophage. This finding suggests that ICE-like protease may be involved in the induction of apoptosis in macrophage by TNF-alpha.