title: Ficolin-A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis.
abstract: Human ficolin-2 (FCN-2) and mouse ficolin-A (FCN-A, a ficolin-2-like molecule in mouse) are activators of the lectin complement pathway, present in normal plasma and usually associated with infectious diseases, but little is known about the role of FCN-A/2 in inflammatory bowel disease (IBD). In our present study, we found that patients with IBD exhibited much higher serum FCN-2 levels than healthy controls. In the dextran sulphate sodium-induced acute colitis mouse model, FCN-A knockout mice showed much milder disease symptoms with less histological damage, lower expression levels of pro-inflammatory cytokines [interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α (TNF-α)], chemokines (CXCL1/2/10 and CCL4) and higher levels of the anti-inflammatory cytokine IL-10 compared with wild-type mice. We demonstrated that FCN-A/2 exacerbated the inflammatory pathogenesis of IBD by stimulating M1 polarization through the TLR4/MyD88/MAPK/NF-κB signalling pathway in macrophages. Hence, our data suggest that FCN-A/2 may be used as a novel therapeutic target for IBD.
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Department of Microbiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Champaign, IL, USA.
authors.forename: Yi-Dan
authors.initials: YD
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology/Hepatology, Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, China.
authors.forename: Jia-Chen
authors.initials: JC
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Wen-Xiu
authors.initials: WX
authors.lastname: Bian
authors.affiliation: Biomedical Translational Research Institute, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000097604:Ficolins
chemical_list: D016207:Cytokines; D037102:Lectins; D051197:Toll-Like Receptor 4; D000097604:Ficolins
keywords: Toll-like receptor 4; ficolin-2; ficolin-A; inflammatory bowel disease; macrophage