Interferon-alpha inhibits Stat5 DNA-binding in IL-2 stimulated primary T-lymphocytes. |
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Authors: | Sven Erickson Sampsa Matikainen Lena Thyrell Olle Sangfelt Ilkka Julkunen Stefan Einhorn Dan Grandér |
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Institution: | Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Hospital and Institute, Stockholm, Sweden. |
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Abstract: | It has previously been shown that IFN-alpha 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-alpha on IL-2 signal transduction was investigated. The IFN-alpha 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-2R alpha. Our results provide a possible molecular link between the prominent antiproliferative effects of IFN-alpha on IL-2 induced T-cell proliferation and the signal transduction pathways emerging from the IL-2 receptor. |
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