Interferon-alpha inhibits Stat5 DNA-binding in IL-2 stimulated primary T-lymphocytes.
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.
Erickson
Sven
S
Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Hospital and Institute, Stockholm, Sweden.
Matikainen
Sampsa
S
Thyrell
Lena
L
Sangfelt
Olle
O
Julkunen
Ilkka
I
Einhorn
Stefan
S
Grandér
Dan
D
D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D053616:Janus Kinase 3; D008894:Milk Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D050799:STAT5 Transcription Factor; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D007376:Interleukin-2; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3