Tumor necrosis factor-alpha mediates antiapoptotic signals partially via p38 MAP kinase activation in human...

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine with many biological effects on a variety of cells. In particular, TNF-alpha has been shown to act as a death or survival factor which mediates apoptosis or antiapoptotic signals in various types of cells. In eosinophils, TNF-alpha has been reported to activate eosinophil functions. However, it is not clearly defined whether TNF-alpha delivers antiapoptotic signals in eosinophils. In order to determine whether TNF-alpha prevents eosinophil apoptosis, we examined the effect of TNF-alpha on eosinophil apoptosis by the survival assay and cell cycle analysis. We also determined whether intracellular MAP kinases (ERKs, Jun kinase/JNK, and p38 MAP kinase) are involved in the TNF-alpha-induced signaling for the prevention of eosinophil apoptosis. We showed that TNF-alpha mediated antiapoptotic signals in human eosinophils in part via activation of p38 MAP kinase, but not via activation of ERKs and JNK. Our data suggest that TNF-alpha/p38 MAP kinase pathways are involved in the regulation of eosinophil survival and, thus, would be important for the development of allergic eosinophil-rich inflammation.