The anti-inflammatory effects of interleukin-4 are not mediated by suppressor of cytokine signalling-1 (SOCS1)
- Author(s)
- Woodward, EA; Prele, CM; Nicholson, SE; Kolesnik, TB; Hart, PH;
- Details
- Publication Year 2010-09,Volume 131,Issue #1,Page 118-127
- Journal Title
- IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- P>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)-alpha production by IL-4. IL-4 suppressed LPS-induced TNF-alpha 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-alpha production by bone-marrow derived macrophages from wild-type mice, Ifn gamma-/- mice and mice lacking SOCS1 (Socs1-/-Ifn gamma-/-). These data suggest that SOCS1 is not involved in the suppression of LPS-induced TNF-alpha production by IL-4.
- Publisher
- WILEY-BLACKWELL
- Keywords
- NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; HUMAN MONOCYTES; PPAR-GAMMA; ALTERNATIVE ACTIVATION; GENE-EXPRESSION; TNF-ALPHA; MACROPHAGE ACTIVATION; AUTOIMMUNE-DISEASE; INSULIN-RESISTANCE
- Publisher's Version
- https://doi.org/10.1111/j.1365-2567.2010.03281.x
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- Refer to copyright notice on published article.
Creation Date: 2010-09-01 12:00:00