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

• Published in: Immunology Vol. 131; no. 1; pp. 118 - 127
• Main Authors: Woodward, Eleanor A, Prêle, Cecilia M, Nicholson, Sandra E, Kolesnik, Tatiana B, Hart, Prue H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.09.2010; Blackwell Publishing Ltd; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Cells, Cultured; Cytokines; endotoxin/lipopolysaccharide; Humans; inflammation; Interferon-gamma - pharmacology; Interleukin-4 - metabolism; Interleukin-4 - pharmacology; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; macrophages/monocytes; Medical research; Mice; Mice, Inbred C57BL; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Original; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signal Transduction; signalling/signal transduction; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins - drug effects; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Tumor Necrosis Factor-alpha - metabolism
• DOI: 10.1111/j.1365-2567.2010.03281.x
• ISSN: 0019-2805

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.