Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.
As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system.
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20003, PR China.
Peipei
P
Ding
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20003, PR China.
Ling
L
Li
Department of Urology, Shanghai Tenth People's Hospital, Shanghai 200072, PR China; Department of Urology, Northern Jiangsu People's Hospital, Yangzhou University, Yangzhou, Jiangsu 225001, PR China.
Tianbao
T
Huang
Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
Chaoqun
C
Yang
Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
Enjie
E
Xu
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20003, PR China.
Na
N
Wang
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20003, PR China.
Long
L
Zhang
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20003, PR China.
Hongyu
H
Gu
Department of Urology, Shanghai Tenth People's Hospital, Shanghai 200072, PR China.
Xudong
X
Yao
Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
Xuhui
X
Zhou
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20003, PR China; Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China. Electronic address: weiguohu@fudan.edu.cn.
Weiguo
W
Hu
D000818:Animals; D003092:Colitis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003183:Complement C6 / Q000008:administration & dosage / Q000172:deficiency* / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D000081208:Hereditary Complement Deficiency Diseases; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
D003183:Complement C6; D015938:Complement Membrane Attack Complex; D016207:Cytokines; D018836:Inflammation Mediators; D003165:Complement System Proteins; D016264:Dextran Sulfate
C6 deficiency; Colitis; Complement; DSS; Inflammatory bowel disease