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The anti-inflammatory effects of interleukin-4 are not mediated by suppressor of cytokine signalling-1 (SOCS1)

Woodward, E.A., Prêle, C.M., Nicholson, S.E., Kolesnik, T.B. and Hart, P.H. (2010) The anti-inflammatory effects of interleukin-4 are not mediated by suppressor of cytokine signalling-1 (SOCS1). Immunology, 131 (1). pp. 118-127.

Free to read: https://doi.org/10.1111/j.1365-2567.2010.03281.x
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Abstract

While it is known that the anti-inflammatory effects of interleukin (IL)-4 require new protein synthesis, the exact mechanisms by which IL-4 suppresses the production of pro-inflammatory cytokines by human monocytes and macrophages is unclear. IL-4 rapidly induced suppressor of cytokine signalling-1 (SOCS1) mRNA and protein, which peaked at 60 min, much earlier than lipopolysaccharide (LPS)-induced SOCS1 mRNA and protein which were consistently maximal 4 hr post-exposure. SOCS1 is a molecule generally considered to be induced for negative feedback of inflammatory processes. We investigated whether the early induction of SOCS1 by IL-4 was responsible for the suppression of LPS-induced tumour necrosis factor (TNF)-α production by IL-4. IL-4 suppressed LPS-induced TNF-α in freshly isolated monocytes at the level of transcription but acted by a different, possibly translational, mechanism in monocytes cultured overnight in macrophage colony-stimulating factor (M-CSF). Despite different modes of regulation by IL-4, the kinetics and magnitude of induction of SOCS1 mRNA and protein by IL-4 in the two cell types were identical. There was no significant difference in the suppression by IL-4 of LPS-induced TNF-α production by bone-marrow derived macrophages from wild-type mice, Ifnγ−/− mice and mice lacking SOCS1 (Socs1−/−Ifnγ−/−). These data suggest that SOCS1 is not involved in the suppression of LPS-induced TNF-α production by IL-4.

Item Type: Journal Article
Publisher: Wiley-Blackwell
Copyright: © 2010 The Authors. Journal Compilation/Blackwell Publishing Ltd
URI: http://researchrepository.murdoch.edu.au/id/eprint/64418
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