Increased expression of protease-activated receptor-2 in mucosal mast cells in Crohn's ileitis

Abstract

Background and aims Activation of protease-activated receptor-2 (PAR-2) may stimulate various events of importance in inflammatory processes, including release of inflammatory mast cell mediators. PAR-2 is frequently up-regulated during inflammatory conditions, but it is not known if the expression is altered in Crohn's disease. The aim of the present study was to investigate the ileal mucosal PAR-2 expression in Crohn's ileitis, with particular emphasis on the expression in ileal mucosal mast cells. Methods Surgical specimens from the distal ileum were collected from patients with Crohn's ileitis and patients with colonic cancer as controls. The overall expression of PAR-2 was investigated by Western blot, and the presence of PAR-2 expressing mucosal mast cells by immunohistochemistry and cell counting. The effect of tumor necrosis factor-α (TNF-α) on the PAR-2 expression in a human mast cell line (HMC-1) was investigated by RT-PCR and immunocytochemistry. Results In Crohn's specimens, the fraction of PAR-2-expressing mucosal mast cells was increased about 2.5 times ( P < 0.001; n = 14) compared with specimens from control patients ( n = 6). No difference was found between inflamed ( n = 6) and uninflamed Crohn's specimens ( P > 0.05; n = 8). Exposure to TNF-α for 48 h up-regulated PAR-2 mRNA and protein expression in the HMC-1 cell line. Conclusion PAR-2 is up-regulated on ileal mucosal mast cells in Crohn's ileitis, possibly due to the action of inflammatory cytokines, such as TNF-α. This may contribute to perpetuating the inflammatory process in the intestinal mucosa in Crohn's ileitis.