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The anti‐inflammatory effects of interleukin‐4 are not mediated by suppressor of cytokine signalling‐1 (SOCS1)
Author(s) -
Woodward Eleanor A.,
Prêle Cecilia M.,
Nicholson Sandra E.,
Kolesnik Tatiana B.,
Hart Prue H.
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03281.x
Subject(s) - suppressor of cytokine signaling 1 , cytokine , lipopolysaccharide , suppressor of cytokine signalling , tumor necrosis factor alpha , biology , monocyte , interleukin , immunology , interleukin 6 , microbiology and biotechnology , signal transduction , suppressor , socs3 , gene , biochemistry , stat3
Summary 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.