Src promotes anti-inflammatory (M2) macrophage generation via the IL-4/STAT6 pathway. (November 2018)

• Record Type: Journal Article
• Authors: Hu, Xiang; Wang, Huamin; Han, Chaofeng; Cao, Xuetao
• Is Part Of: Cytokine. Volume 111(2018)
• Page Start: 209
• Page End: 215
• Publication Date: 2018-11
• Subjects: Macrophage polarization -- Inflammation -- Src -- STAT6; Arg1 Arginase -- BMDMs Bone Marrow-Derived Macrophages -- C/EBPβ CCAAT/enhancer-binding Protein beta -- CREB cAMP-Response Element Binding protein -- DSS Dextran Sulfate Sodium -- Fizz1 Found in inflammatory zone 1 -- IL Interleukin -- iNOS inducible Nitric Oxide Synthase -- IP immunoprecipitation -- Jak1 Janus Kinase 1 -- Mr1 or CD206 Mannose receptor 1 -- NO Nitric Oxide -- PAMPs Pathogen-Associated Molecular Patterns -- PRRs Pattern Recognition Receptors -- ROS Reactive Oxygen Species -- Ym1 Chitinase 3-like 3; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.08.030
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Src contributes to the generation of anti-inflammatory M2 macrophages in colitis. Src promotes IL-4-induced Arg1 expression and inhibits IFN-γ-induced iNOS expression. Src promotes M2 macrophage marker expression via STAT6 and Jak1. Abstract: The balance between pro-inflammatory and anti-inflammatory macrophage generation, a process known as polarization, is critical for immune homoeostasis. Identifying the molecular mechanisms underlying polarization and the generation of anti-inflammatory macrophages is an area of high current interest. Our previous work has demonstrated that integrin CD11b promotes IL-10 production in macrophages by activating the Sarcoma gene (Src), yet whether and how Src modulates anti-inflammatory macrophages is not known. Here we show that Src inhibitor (Dasatinib)-treated mice were highly susceptible to dextran sulfate sodium (DSS)-induced colitis, with a much more sever inflammation response, accompanying by high TNF-α, and low IL-10 expression. Inhibition of Src enhanced the expression of pro-inflammatory macrophage marker inducible nitric oxide synthase (iNOS), but reduced the expression of anti-inflammatory macrophage marker arginase1 (Arg1) in both intestinal macrophages and bone marrow-derived macrophages (BMDMs). Overexpression of constitutively activated Src promoted IL-4-induced expression of Arg1 through STAT6 phosphorylation, and Jak1 was also involved in this process. Our results reveal that the IL-4-Src-STAT6 pathway plays a major role in polarizing anti-inflammatory macrophage generation and suggest a potential anti-inflammatory role for Src in inflammatory diseases.