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

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.

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 (CGRP_8-37 ), and RAMP1 knockout (^-/- ) mice. Pathological changes in the mucosa were assessed, and inflammatory cells and cytokine levels were measured.

The severity of inflammation in DSS-induced colitis increased markedly in CGRP_8-37 -treated mice and RAMP1^-/- mice compared with WT mice. RAMP1^-/- mice showed more severe damage compared with CGRP_8-37 -treated mice. The number of periodic acid-Schiff-positive cells decreased in CGRP_8-37 -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.

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.