Mechanism of inhibition of eosinophil activation by transforming growth factor-β - Inhibition of Lyn, MAP, Jak2 kinases and STAT1 nuclear factor

Konrad Pazdrak, Louis Justement, Rafeul Alam

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    59 Citations (Scopus)

    Abstract

    The activation of eosinophils by IL-5 plays a crucial role in the pathogenesis of allergic and parasitic disorders. IL-5 has recently been shown to activate Lyn and Jak2 tyrosine kinases, MAP kinases, and STAT1 nuclear factor. We have previously reported that TGF-β blocks the IL-5-induced activation of eosinophils. In this study, we investigated the effect of TGF-β on the IL-5-induced signaling molecules in eosinophils. Purified eosinophils from mildly allergic patients were preincubated with TGF-β and then stimulated with IL-5. The cell lysates were then immunoprecipitated and blotted with antiphosphotyrosine Abs. The activity of the kinases was further studied in the immune-complex kinase assay. We found that TGF-β inhibited the tyrosine phosphorylation of multiple proteins in eosinophils. The identity of some of the proteins was established by immunoprecipitation. We found that TGF-β inhibited tyrosine phosphorylation of Lyn, Jak2, and a 44-kDa MAP kinase. In further experiments, it blocked the activation of the above kinases as determined by immune-complex kinase assay. TGF-β also inhibited phosphorylation of the STAT1 (p91) nuclear protein in eosinophils. We believe that the inhibition of Lyn, Jak2, MAP kinase, and the STAT1 nuclear protein may underlie the inhibitory activity of TGF-β on eosinophils.

    Original languageEnglish (US)
    Pages (from-to)4454-4458
    Number of pages5
    JournalJournal of Immunology
    Volume155
    Issue number9
    StatePublished - 1995

    Fingerprint

    Transforming Growth Factors
    Eosinophils
    Interleukin-5
    Phosphotransferases
    Phosphorylation
    Nuclear Proteins
    Antigen-Antibody Complex
    Tyrosine
    STAT1 Transcription Factor
    Mitogen-Activated Protein Kinase Kinases
    Immunoprecipitation
    Protein-Tyrosine Kinases
    Proteins

    ASJC Scopus subject areas

    • Immunology

    Cite this

    Mechanism of inhibition of eosinophil activation by transforming growth factor-β - Inhibition of Lyn, MAP, Jak2 kinases and STAT1 nuclear factor. / Pazdrak, Konrad; Justement, Louis; Alam, Rafeul.

    In: Journal of Immunology, Vol. 155, No. 9, 1995, p. 4454-4458.

    Research output: Contribution to journalArticle

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