Local chemerin levels are positively associated with DSS-induced colitis but constitutive loss of CMKLR1 does not protect against development of colitis.
Inflammatory bowel disease (IBD) is a family of disorders including ulcerative colitis and Crohn's disease that are characterized by chronic and relapsing intestinal inflammation. Increased production of proinflammatory mediators, possibly combined with low expression of anti-inflammatory mediators, is thought to promote the development and progression of IBD. In the current study, we demonstrate that expression, secretion, and processing of chemerin, a potent chemoattractant for cells expressing chemokine-like receptor 1 (CMKLR1), increased in the cecum and colon along a gradient positively associated with the severity of inflammation in dextran sodium sulfate (DSS)-induced colitis. We also show that levels of circulating bioactive chemerin increased following DSS treatment. At both 6-8 and 14-16 weeks of age, CMKLR1 knockout mice developed signs of clinical illness more slowly than wild type and had changes in circulating cytokine levels, increased spleen weight, and increased local chemerin secretion following DSS treatment. However, knockout mice ultimately developed similar levels of clinical illness and local inflammation as wild type. Finally, contrary to previous reports, intraperitoneal injection of bioactive chemerin had no effect on the severity of DSS-induced colitis. This suggests that local chemerin levels have a greater impact than circulating levels in the pathogenesis of colitis. Considered altogether, bioactive chemerin represents a novel biomarker for IBD severity, although strategies to modulate endogenous chemerin signaling other than chronic CMKLR1 loss are necessary in order to exploit chemerin as a therapeutic target for the treatment of IBD.
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Helen J
HJ
Dranse
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Jillian L
JL
Rourke
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Andrew W
AW
Stadnyk
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada csinal@dal.ca.
Christopher J
CJ
Sinal
Adipokine; CMKLR1; chemerin; colitis; inflammatory bowel disease