Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohnʼs disease

Abstract

Serum collection and IBD biobank supported by the Bundesministerium für Bildung und Forschung (German Ministry of Education and Research), Kompetenznetz chronisch entzündliche Darmerkrankungen (Competence network "Inflammatory Bowel Disease"). AbstractChemerin is an adipose tissue-secreted protein that stimulates chemotaxis of cells of the innate immune system. Inflammatory bowel disease (IBD) is linked to an impaired immune response and, therefore, we hypothesized that systemic chemerin may be altered in IBDpatients. Serum was collected from patients with Crohn´s disease (CD, 230 patients), ulcerative colitis (UC, 80 patients) and healthy controls (HC, 80 probands). Chemerin and adiponectin, which has already been measured in the serum of similar cohorts by others, were determined by ELISA. Sytemic chemerin concentrations were significantly elevated in serum of CD and UC patients compared to HC, and were also found to be higher in the serum of males with CD compared to males with UC. Adiponectin levels were lower in CD compared to UC and HC with similar circulating concentrations. In serum of male but not female patients chemerin levels were higher in UC patients with active disease whereas adiponectin was reduced. In CD elevated chemerin was associated with remission in males only.Treatment with corticosteroids was linked to elevated adiponectin in male CD patients and higher chemerin in female UC patients. Unlike adiponectin that is elevated in female serum in all cohorts analysed, chemerin was only higher in the serum of female UC patients.These data indicate that the levels of circulating chemerin are elevated in patients suffering from UC and CD whereas adiponectin is reduced in the latter. Relations of the systemic 2 concentrations of these adipokines to disease activity and treatment are disease-and genderspecific.3

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

“…In contrast, we and others (14) show that ChemR23 mRNA levels increase in human monocytes and macrophages after stimulation with LPS or the inflammatory cytokines TNF-a and IFN-g, suggesting that there are differences between mouse and human in the regulation and eventual function of ChemR23. This notion would be supported by the fact that chemerin has ChemR23-dependent antiinflammatory and protective effects in some mouse models of inflammation (39,40), whereas in humans, chemerin was shown to induce inflammatory signaling in chondrocytes (41) and increased chemerin concentrations were associated with pathologies connected with chronic and systemic inflammation (19,21,(42)(43)(44). The differential expression pattern of ChemR23 on stimulated macrophages and the possible opposite effect of chemerin on inflammation between mouse and human may indicate that the role of ChemR23 signaling differs between the two species.…”

“…Secreted by mature adipocytes, it stimulates preadipocytes to differentiation. Increased serum levels of chemerin have been associated with chronic inflammatory diseases (19,20), coronary artery disease (21), the metabolic syndrome, and obesity (22). There is indication that high chemerin production in obese adipose tissue (23) might contribute to the increased infiltration of macrophages observed in obese adipose tissue leading to low-level inflammation (24).…”

Chemerin, a novel player in inflammatory bowel disease

“…3 Chemerin, which is mainly expressed in adipocytes and hepatocytes, is also present at higher concentrations in serum from IBD patients. [4][5][6] Chemerin is an attractant for immune cells and may play a role in the recruitment of tissue macrophages. 4 Chemerin produced by human fetal intestinal epithelial cells constitutes most of the chemotactic macrophage activity observed in cultured fetal intestinal epithelial cells.…”

“…6 In colon biopsies of patients with ulcerative colitis, the expression of chemerin is higher in inflamed tissues and, importantly, is further increased in more severely inflamed tissues. 9 Colon cells isolated from DSS-treated mice release chemerin at levels consistent with disease severity.…”

“…Therefore, only locally produced chemerin is associated with disease severity in rodent and human IBD. 6,9 Higher circulating chemerin levels in IBD may result from increased intestinal or colonic secretion. Furthermore, pro-inflammatory cytokines induce adipocytes to express chemerin but have no effect on hepatocytes 4,5 (Figure 1).…”