title: Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization.
abstract: Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease (IBD); however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin (aa17-156) aggravated the severity of dextran sulfate sodium (DSS)-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-α and interferon (IFN-γ). Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis (UC) patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Shanghai, China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Shanghai, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Shanghai, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yue
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Shanghai, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Shanghai, China.
authors.forename: Bingji
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Shanghai, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zou
authors.affiliation: 1] Department of Immunology, School of Basic Medical Sciences, Shanghai, China [2] Biotherapy Research Center, Fudan University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: He
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D020848:Chimerin 1 / Q000008:administration & dosage*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage*; D050800:STAT6 Transcription Factor / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D020848:Chimerin 1; D016207:Cytokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D010446:Peptide Fragments; C413576:Retnla protein, mouse; D050800:STAT6 Transcription Factor; D016264:Dextran Sulfate; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases; C544448:Arg1 protein, mouse; D001119:Arginase
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