Regulation of galectin‐3 function in mucosal fibroblasts: potential role in mucosal inflammation
Recently we identified galectin‐3 (gal‐3), which is secreted by colonic epithelial cells (CEC), to be a strong activator of colonic lamina propria fibroblasts (CLPF). Modulation of CLPF function may play a role during stricture and fistula formation in inflammatory bowel disease (IBD). Therefore, we investigated further the expression of gal‐3 and effects on CLPF. The aim of this study is to perform a direct comparison of gal‐3 between tissue from healthy controls and from patients with either Crohn's disease (CD) or ulcerative colitis (UC). CEC, CLPF and intestinal macrophages (IMAC) were isolated from control and IBD colonic tissue. Interleukin‐8 secretion as a readout of CLPF activation was quantified by enzyme‐linked immunosorbent assay. Gal‐3 in cell cultures and tissue samples was evaluated by Western blot, immunofluorescence and immunohistochemistry. CLPF‐migration was assayed in the 48‐well modified Boyden chamber. Gal‐3 expression was found in all segments of the colon. In the terminal ileum, less gal‐3 was found compared with the colon. Immunohistochemistry and immunofluorescence revealed a homogenous distribution of gal‐3 in CEC and IMAC of control mucosa and UC. However, significantly less gal‐3 was found in IMAC from CD patients. In CD fistulae and stenoses, gal‐3 expression was reduced significantly and barely detectable. In co‐incubation studies lactose reduced significantly the CLPF‐stimulatory potential of gal‐3, indicating that the C‐terminal domain of gal‐3 is responsible for CLPF activation. Gal‐3 stimulated CLPF migration in CLPF derived from fistulae. In conclusion, gal‐3 expression is down‐regulated in CD‐fistulae and stenoses as well as in IMAC in CD patients. Gal‐3 induces migration of CLPF derived from fistulae. Its role for stricture and fistula formation warrants further investigation.