TITLE

Crucial role of the melanocortin receptor MC1R in experimental colitis

AUTHOR(S)
Maaser, C.; Kannengiesser, K.; Specht, C.; Lügering, A.; Brzoska, I.; Luger, T. A.; Domschke, W.; Kucharzik, T.
PUB. DATE
October 2006
SOURCE
Gut;Oct2006, Vol. 55 Issue 10, p1415
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: α-Melanocyte stimulating hormone (αMSH) is known to exert anti-inflammatory effects, for example in murine DSS (dextran sodium sulphate induced) colitis. The anti-inflammatory functions of αMSH are mediated by the melanocortin1-receptor (MC1R) in an autoregulatory loop. The aim of this study was therefore to determine whether a breakdown of the αMSH-MC1R pathway leads to worsening of disease. Methods: Experimental colitis was induced in mice with a frameshift mutation in the MC1R gene (MC1Re/e), C57BL/6 wild type mice, and MC1Re/e-C57BL/6 bone marrow chimeras. The course of inflammation was monitored by weight loss, histological changes in the colon, and myeloperoxidase activity. In addition, MC1R expression was analysed in intestinal epithelial cells. Results: While the colon of untreated MC1Re/e appeared normal, the course of DSS-colitis in MC1Re/e mice was dramatically aggravated, with a significantly higher weight loss and marked histological changes compared to C57BL/6WT. The inflammation eventually led to death in all MC1 Re/e, while all C57BL/6WT survived. Similar observations were detected in a transmissible murine colitis model induced by Citrobacter rodentium. Infected MC1Re/e showed delayed clearance of infection. To determine whether missing haematopoietic cell expressed MC1R was responsible, DSS colitis was induced in MC1Re/e-C57BL/6 bone marrow chimeras. MC1Re/e mice receiving MC1R+ bone marrow showed a similar course of inflammation to non-transplanted MC1Re/e. Likewise, transplantation of MC1R bone marrow into C57BL/6WT mice did not lead to any worsening of disease. Conclusions: This is the first study to show a functional role ofMC1R in intestinal inflammation. The data suggest a pivotal role of non-haematopoietic cell expressed MC1R in the host's response to pathogenic stimuli.
ACCESSION #
22659583

 

Related Articles

  • Active Nanofibrous Membrane Effects on Gingival Cell Inflammatory Response. Morand, David-Nicolas; Huck, Olivier; Keller, Laetitia; Jessel, Nadia; Tenenbaum, Henri; Davideau, Jean-Luc // Materials (1996-1944);2015, Vol. 8 Issue 10, p7217 

    Alpha-melanocyte stimulating hormone (α-MSH) is involved in normal skin wound healing and also has anti-inflammatory properties. The association of α-MSH to polyelectrolyte layers with various supports has been shown to improve these anti-inflammatory properties. This study aimed to...

  • The Role of Bacteria in the Pathogenesis of Ulcerative Colitis. Sasaki, Maiko; Klapproth, Jan-Michael A. // Journal of Signal Transduction;2012, p1 

    Factors implicated in the pathophysiology of ulcerative colitis (UC) are an abnormal immune response, defect in intestinal epithelial barrier function, and gut microbiota. Currently, it is unclear whether specific bacterial strains are responsible for the induction of intestinal inflammation,...

  • Histopathological Changes in the Gastrointestinal Tract Due to Medications: An Update for the Surgical Pathologist (Part II of II). De Petris, Giovanni; Gatius Caldero, Sonia; Chen, Longwen; Xiao, Shu-Yuan; Dhungel, Bal M.; Wendel Spizcka, Amy J.; Lam-Himlin, Dora // International Journal of Surgical Pathology;May2014, Vol. 22 Issue 3, p202 

    In keeping with the stated goal of providing the surgical pathologist with tools to recognize abnormalities of the gastrointestinal (GI) tract due to drugs (AGIDS), in part II of this review we embark in a more organ-based description of AGIDS. Adequate space is given to the numerous adverse...

  • NSAID Colitis--Resolving a Diagnostic Dilemma? Koch, Timothy R.; Johnson, David // American Journal of Gastroenterology;Mar2001, Vol. 96 Issue 3, p914 

    It has become increasingly clear that nonsteroidal anti-inflammatory drugs may cause damage not only to the upper gastrointestinal tract but also to the small and large intestine. Although the colon may be readily investigated by endoscopy, drug-induced lesions are not well known, probably...

  • Epithelial Expression of Vasoactive Intestinal Peptide in Ulcerative Colitis: Down-Regulation in Markedly Inflamed Colon. Jönsson, Maria; Norrgård, Örjan; Forsgren, Sture // Digestive Diseases & Sciences;Feb2012, Vol. 57 Issue 2, p303 

    Background: Vasoactive intestinal peptide (VIP) has a number of important effects in intestinal physiology and pathology, including in ulcerative colitis (UC). The expression patterns of the predominant VIP receptor in the mucosa (the VPAC1 receptor) are unknown for the mucosa in UC. It is...

  • Iridoid Glycosides Fraction of Folium syringae Leaves Modulates NF-&kgr;B Signal Pathway and Intestinal Epithelial Cells Apoptosis in Experimental Colitis. Xin Liu; Jian Ming Wang // PLoS ONE;2011, Vol. 6 Issue 9, p1 

    Background and Aims: Iridoid glycosides (IG), the major active fraction of F. syringae leaves has been demonstrated to have strong anti-inflammatory properties to ulcerative colitis (UC) in our previous study. The aim of this study was to investigate whether IG modulates the inflammatory...

  • Clinical and histological predictors of response to medical therapy in collagenous colitis. Abdo, A.; Raboud, J.; Freeman, H.J.; Zetler, P.; Tilley, J.; Chaun, H.; Whittaker, J.S.; Amar, J.; Halparin, L.; Enns, R. // American Journal of Gastroenterology;May2002, Vol. 97 Issue 5, p1164 

    OBJECTIVES:Collagenous colitis (CC) is an uncommon form of inflammatory bowel disease. The response to typical medical therapies (antimotility agents, 5-aminosalicylic acid [5-ASA], and corticosteroids) is variable. We aimed to determine if there are clinical or histological variables that can...

  • Rofecoxib: A Viewpoint by Richard H. Hunt. Hunt, R.H. // Drugs;Sep1999, Vol. 58 Issue 3, p506 

    Comments on a study on the use of the nonsteroidal anti-inflammatory drug rofecoxib in gastrointestinal disease. Details on the tolerability of rofecoxib; Mechanism of action; Background on nonsteroidal anti-inflammatory drugs.

  • Erratum to: The Interplay Between NSAIDs and Candida albicans on the Gastrointestinal Tract of Guinea Pigs. Nadăş, George; Taulescu, Marian; Ciobanu, Lidia; Fiţ, Nicodim; Flore, Chirilă; Răpuntean, Sorin; Bouari, Cosmina; Catoi, Cornel // Mycopathologia;Aug2013, Vol. 176 Issue 1/2, p171 

    A correction to the article "The Interplay Between NSAIDs and Candida albicans on the Gastrointestinal Tract of Guinea Pigs" published in a previous issue is presented.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics