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

Oncogene volume 19, pages 5898–5905 (2000)Cite this article

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.

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Acknowledgements

The authors would like to thank M Zohair and J Giron-Michel for excellent assistance with confocal microscopy and Drs M Souyri, JP Rosa, B Peault and M Tovey for their critical review of the manuscript. C Doucet had fellowships from Ligue Nationale Française contre le Cancer du Val de Marne and Association pour la Recherche sur le Cancer (ARC). This work was supported by NRB-Vaincre le Cancer.

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  1. B Azzarone

    Present address: INSERM U506, Hôpital Paul Brousse, 16, Av. P.V., Couturier, 94807, Villejuif, France

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  1. INSERM U268, Hôpital Paul Brousse, 16, Av. P.V., Couturier, 94807, Villejuif, France

    C Doucet, C Doucet, C Jasmin & B Azzarone

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Doucet, C., Jasmin, C. & Azzarone, B. Unusual interleukin-4 and -13 signaling in human normal and tumor lung fibroblasts. Oncogene 19, 5898–5905 (2000). https://doi.org/10.1038/sj.onc.1203933

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