RAMP1 suppresses mucosal injury from dextran sodium sulfate-induced colitis in mice.

BACKGROUND AND AIMS: Calcitonin gene-related peptide (CGRP) is thought to be involved in the modulation of intestinal motility. CGRP receptor is composed of receptor activity-modifying protein (RAMP) 1 combined with calcitonin receptor-like receptor (CRLR) for CGRP. The study investigated the role of CGRP in mice with experimentally induced colitis.

METHODS: The study used dextran sodium sulfate (DSS) to induce colitis in mice. The study compared the severity of colitis in wild-type (WT) mice, mice treated with a CGRP receptor antagonist (CGRP8-37 ), and RAMP1 knockout ((-/-) ) mice. Pathological changes in the mucosa were assessed, and inflammatory cells and cytokine levels were measured.

RESULTS: The severity of inflammation in DSS-induced colitis increased markedly in CGRP8-37 -treated mice and RAMP1(-/-) mice compared with WT mice. RAMP1(-/-) mice showed more severe damage compared with CGRP8-37 -treated mice. The number of periodic acid-Schiff-positive cells decreased in CGRP8-37 -treated mice compared with WT mice and was even further decreased in RAMP1(-/-) mice. RAMP1 was expressed by macrophages, mast cells, and T-cells. RAMP1(-/-) mice exhibited excessive accumulation of macrophages and mast cells into the colonic tissue with increased levels of tumor necrosis factor-α and interleukin-1β as compared with WT mice. Infiltration of T-cells into the colonic mucosa, which was associated with the expression of T helper (Th) cytokines including Th1 (interferon gamma) and Th17 (IL-17), was augmented in RAMP1(-/-) mice.

CONCLUSIONS: The findings of this study suggest that RAMP1 exerted mucosal protection in DSS-induced colitis via attenuation of recruitment of inflammatory cells and of pro-inflammatory cytokines.