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 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.
Tsukahara
K
K
Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
Nakao
A
A
Hiraguri
M
M
Miike
S
S
Mamura
M
M
Saito
Y
Y
Iwamoto
I
I
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
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases