title: RAMP1 suppresses mucosal injury from dextran sodium sulfate-induced colitis in mice.
abstract: OBJECTIVE
  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.
authors: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.|Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Noriko
authors: N
authors: Kawashima-Takeda
authors: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.|Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Yoshiya
authors: Y
authors: Ito
authors: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.|Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Nobuyuki
authors: N
authors: Nishizawa
authors: Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan.
authors: Rei
authors: R
authors: Kawashima
authors: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Kiyoshi
authors: K
authors: Tanaka
authors: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: Kazutake
authors: K
authors: Tsujikawa
authors: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Masahiko
authors: M
authors: Watanabe
authors: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Masataka
authors: M
authors: Majima
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058262:Receptor Activity-Modifying Protein 1 / Q000378:metabolism / Q000502:physiology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C545505:Ramp1 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; DSS; RAMP1; colitis