Ultraviolet radiation inhibits interleukin-2-induced tyrosine phosphorylation and the activation of STAT5 in T lymphocytes.
UV radiation was recently found to hinder interferon-gamma from exerting its biological effects by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)-1, a crucial signal transducing protein in the interferon-gamma pathway. Because this activity by UV may contribute to its immunosuppressive properties we studied whether this is specific for STAT1 or whether UV also affects other members of the STAT family. STAT5 is crucially involved in signaling of interleukin (IL)-2, enabling up-regulation of the IL-2 receptor alpha chain, an essential component of the high affinity IL-2 receptor. Exposure of the murine T cell line CTLL to IL-2 caused tyrosine phosphorylation of STAT5 that was remarkably reduced when cells were exposed to UV. Accordingly, STAT5 binding activity was significantly impaired in UV-exposed cells. In contrast, IL-2-induced tyrosine phosphorylation of the kinases Jak1 and Jak3 located upstream of STAT5 was not affected by UV. The effect of UV on STAT5 phosphorylation was antagonized by orthovanadate, implying involvement of a phosphatase in this process. Accordingly, up-regulation of the IL-2 receptor alpha chain was reduced in cells that were treated with IL-2 plus UV. Because STAT5-mediated IL-2 effects are vital for normal immune functions, inhibition of STAT5 signaling by UV may contribute to its well known immunosuppressive properties.
Kulms
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Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University Münster, Von-Esmarchstrasse 58, D-48149 Münster, Germany.
Schwarz
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D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000528:radiation effects; D015534:Trans-Activators / Q000378:metabolism* / Q000528:radiation effects; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D014638:Vanadates / Q000494:pharmacology
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D019000:Phosphotyrosine; D014638:Vanadates