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

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 o r antiapoptotic signals in various types of cells. In eosinophils, TNF-alph a has been reported to activate eosinophil functions. However, it is not cl early defined whether TNF-alpha delivers antiapoptotic signals in eosinophi ls. 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 MA P kinases (ERKs, Jun kinase/JNK, and p38 MAP kinase) are involved in the TN F-alpha-induced signaling for the prevention of eosinophil apoptosis. We sh owed that TNF-alpha mediated antiapoptotic signals in human eosinophils in part via activation of p38 MAP kinase, but not via activation of ERKs and J NK. Our data suggest that TNF-alpha/p38 MAP kinase pathways are involved in the regulation of eosinophil survival a nd, th us, would be important for the development of allergic eosinophil-rich inflammation.