TNF-alpha induced altered signaling mechanism in human neutrophil.

In the present study we investigated the TNF-alpha induced signal transduction mechanism in human neutrophil. Exogenously added TNF-alpha affects both PKC activity and its translocation from cytosol to the membrane. Endogenous protein phosphorylation pattern is inhibited in TNF-alpha induced neutrophil in Ca-dependent and Ca-independent manner, including a major 47 and 66 kDa cytosolic proteins, which may be implicated in superoxide anion generation. However TNF-alpha dose dependently enhances the expression of zeta-PKC isotype but not the beta-PKC. Morphology and cell cytotoxicity are studied in TNF-alpha treated neutrophil to understand the TNF-alpha induced cell death or apoptosis and these experiment is further confirmed by DNA fragmentation analysis. These results clearly demonstrate that TNF-alpha induces cellular death of human neutrophil at least in part by enhanced expression of Ca-independent zeta-PKC. These observations provide an insight towards understanding the function of zeta-PKC in apoptotic pathway.