Resistin-like molecule β regulates intestinal mucous secretion and curtails TNBS-induced colitis in mice

Background: Resistin and resistin-like molecule (RELM)β comprise a novel class of cysteine-rich proteins secreted into the circulation implicated in hepatic insulin resistance and inflammation. RELMβ is specifically produced by intestinal goblet cells but regulation of its expression and much of its local function are not elucidated. RELMβ has been suggested to regulate colonic inflammation susceptibility, which is dependent on the mucosal barrier integrity. Methods: In this work we explored the physiopathological role of RELMβ in the colon. Among agents tested, carbachol and gastrin were strong inhibitors of RELMβ mRNA accumulation. We examined the effect of recombinant RELMβ on mucin secretion by human mucus-secreting HT29-Cl.16E cells in culture and by mouse colonic goblet cells in vivo. Results: RELMβ upregulated MUC2 and M1/MUC5AC gene expression in HT29-Cl.16E cells. RELMβ enhanced M1/MUC5AC secretion by human colonic HT29-Cl.16E cells and MUC2 secretion by murine intestinal goblet cells. RELMβ exerted its action exclusively on the apical side of HT29-Cl.16E cells, in agreement with its luminal mucosecretagogue effect in mice. Its action required calcium, protein kinase C, tyrosine kinases, and extracellular-regulated protein kinase activities and was synergized by carbachol. An intracolonic RELMβ challenge was performed in the trinitrobenzene sulfonic acid (TNBS)-murine model of colitis and macroscopic and histological scores were monitored. The macroscopic and histopathological severity of TNBS-induced colitis was significantly attenuated by RELMβ pretreatment. Conclusions: A direct participation in maintaining the mucosal defense barrier can be ascribed to RELMβ in line with a regulatory role in intestinal inflammation. (Inflamm Bowel Dis 2008)