title: The complement anaphylatoxin C3a receptor (C3aR) contributes to the inflammatory response in dextran sulfate sodium (DSS)-induced colitis in mice.
abstract: Inflammatory bowel diseases are a critical public health issue, and as treatment options remain limited, there is a need to unravel the underlying pathomechanisms in order to identify new therapeutic targets. Complement activation was found in patients suffering from inflammatory bowel disease, and the complement anaphylatoxin C5a and its receptor C5aR have been implicated in disease pathogenesis in animal models of bowel inflammation. To further characterize complement-related pathomechanisms in inflammatory bowel disease, we have investigated the role of the anaphylatoxin C3a receptor in acute dextran sulfate sodium-induced colitis in mice. For this, colitis was induced in C3a receptor-deficient BALB/c and C57BL/6 mice, and disease severity was evaluated by clinical and histological examination, and by measuring the mRNA expression or protein levels of inflammatory mediators in the tissue. C3a receptor deficiency was partially protective in BALB/c mice, which had significantly reduced weight loss, clinical and histological scores, colon shortening, and CXCL-1/KC mRNA, myeloperoxidase and interleukin-6 tissue levels compared to the corresponding wild type mice. In C57BL/6 mice the differences between wild type and C3a receptor-deficient animals were much smaller and reached no significance. Our data demonstrate that the contribution of C3a receptor to disease pathogenesis and severity of dextran sulfate sodium-induced colitis in mice depends on the genetic background. Further studies will be required to clarify whether targeting of C3a receptor, possibly in combination with C5a receptor, might be considered as a therapeutic strategy for inflammatory bowel disease.
authors: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors: Elisabeth
authors: E
authors: Wende
authors: Robert
authors: R
authors: Laudeley
authors: André
authors: A
authors: Bleich
authors: Eva
authors: E
authors: Bleich
authors: Rick A
authors: RA
authors: Wetsel
authors: Silke
authors: S
authors: Glage
authors: Andreas
authors: A
authors: Klos
mesh_terms: D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D003167:Complement Activation / Q000276:immunology; D015926:Complement C3a / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D005786:Gene Expression Regulation; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011951:Receptors, Complement / Q000172:deficiency / Q000378:metabolism*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D011951:Receptors, Complement; C085567:complement C3a receptor; D015926:Complement C3a; D016264:Dextran Sulfate; D009195:Peroxidase
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