RAMP1 suppresses mucosal injury from dextran sodium sulfate-induced colitis in mice
| Autor: | Rei Kawashima, Kiyoshi Tanaka, Masahiko Watanabe, Masataka Majima, Noriko Kawashima-Takeda, Nobuyuki Nishizawa, Yoshiya Ito, Kazutake Tsujikawa |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Inflammation Calcitonin gene-related peptide 03 medical and health sciences 0302 clinical medicine Intestinal mucosa Internal medicine Medicine Interferon gamma Colitis Hepatology business.industry Gastroenterology medicine.disease 030104 developmental biology Endocrinology Cytokine RAMP1 Immunology 030211 gastroenterology & hepatology Tumor necrosis factor alpha medicine.symptom business medicine.drug |
| Zdroj: | Journal of Gastroenterology and Hepatology. 32:809-818 |
| ISSN: | 0815-9319 |
| DOI: | 10.1111/jgh.13505 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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