Unusual interleukin-4 and -13 signaling in human normal and tumor lung fibroblasts

C. Doucet, C. Jasmin, B. Azzarone

Research output: Contribution to journalArticle

Abstract

IL-4 and IL-13 act on human lung fibroblasts through specific receptors differing in their composition. Indeed, the γc chain is constitutively expressed in tumor lung myofibroblast but not in normal cells. Here, we have analysed the signal transduction induced by IL-4 and IL-13 in both cell types, in order to better understand the molecular mechanisms underlying tumor stromal development. The IL-4Rα chain is constitutively phosphorylated and pre-associated with the JAK1 protein in both cell types. In normal cells, we detected the activation of the classic IRS-2 or JAK1/STAT6 pathways, the phosphorylation of JAK2, while Tyk2 was constitutively phosphorylated and not modified by both cytokines. In addition to these pathways, in lung tumor myofibroblasts, IL-4 and IL-13 induced the phosphorylation of JAK3 and increased the phosphorylation of Tyk2. Interestingly, in both cell types IL-4 and IL-13 triggered an unusual pattern of STAT1 and STAT3 activation. These events probably correspond to a tissue-specific signaling important for the immunoregulatory functions of airways fibroblasts. Indeed, the inflammatory-like pattern of STATs signaling triggered by IL-4 and IL-13 in these cells may favor the homing of inflammatory and/or metastatic cells. In lung myofibroblasts, these properties could be modified through the different pattern of JAK activation.

Original languageEnglish
Pages (from-to)5898-5905
Number of pages8
JournalOncogene
Volume19
Issue number51
DOIs
Publication statusPublished - Nov 30 2000

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Keywords

  • IL-4/IL-13
  • Lung fibroblasts
  • Myofibroblasts
  • Signal transduction

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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