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

Int Arch Allergy Immunol. 1999:120 Suppl 1:54-9. doi: 10.1159/000053596.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cells, Cultured
  • Eosinophils / metabolism
  • Eosinophils / pathology*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism*
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases