title: Tumor necrosis factor-alpha mediates antiapoptotic signals partially via p38 MAP kinase activation in human eosinophils.
abstract: 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.
authors.affiliation: Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsukahara
authors.forename: A
authors.initials: A
authors.lastname: Nakao
authors.forename: M
authors.initials: M
authors.lastname: Hiraguri
authors.forename: S
authors.initials: S
authors.lastname: Miike
authors.forename: M
authors.initials: M
authors.lastname: Mamura
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: I
authors.initials: I
authors.lastname: Iwamoto
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases