TAILIEUCHUNG - Báo cáo Y học: Interferon-alpha inhibits Stat5 DNA-binding in IL-2 stimulated primary T-lymphocytes

It has previouslybeen shown that IFN-ais apotent inhibitor of IL-2 induced proliferation in primary T-lymphocytes, by selectively abrogating the downstream e ects of IL-2 on the core cell cycle machinery regulating the G1/S transition. Theoretically this could be mediated through cross-talk between the signalling cascades activated by these cytokines, as several signalling components are known to be shared. | Eur. J. Biochem. 269 29 37 2002 FEBS 2002 Interferon-alpha inhibits Stat5 DNA-binding in IL-2 stimulated primary T-lymphocytes Sven Erickson1 Sampsa Matikainen2 I Lena Thyrell1 Olle Sangfelt1 Ilkka Julkunen2 Stefan Einhorn1 and Dan Grander1 1 Department of Oncology and Pathology Cancer Centre Karolinska CCK Karolinska Hospital and Institute Stockholm Sweden department of Virology Mannerheimintie 166 Helsinki Finland It has previously been shown that IFN-a is a potent inhibitor of IL-2 induced proliferation in primary T-lymphocytes by selectively abrogating the downstream effects of IL-2 on the core cell cycle machinery regulating the G1 S transition. Theoretically this could be mediated through cross-talk between the signalling cascades activated by these cytokines as several signalling components are known to be shared. IL-2 activates multiple signalling pathways that are important for T-cell proliferation and differentiation. In the present study the effects of IFN-a on IL-2 signal transduction was investigated. The IFN-a induced inhibition of IL-2 induced proliferation in activated T-lymphocytes was associated with a suppressed Jak3 protein expression as well as an inhibited prolonged Stat5 DNA binding and a partially reduced expression of the Stat5 inducible gene IL-2Ra. Our results provide a possible molecular link between the prominent antiproliferative effects of IFN-a on IL-2 induced T-cell proliferation and the signal transduction pathways emerging from the IL-2 receptor. Keywords interferon-alpha T-lymphocytes Stat5 interleukin-2 proliferation. Interferons IFNs constitute a family of proteins rst isolated because of their antiviral abilities 1 . Today IFNs are known to be therapeutically effective in the treatment of a number of malignancies 2 viral diseases as well as in immunorelated disorders such as multiple sclerosis. IFNs mechanism of action in these diseases is unclear but its well known ability to inhibit proliferation has been suggested to be of

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