Crucial role of the melanocortin receptor MC1R in experimental colitis

Maaser, C.; Kannengiesser, K.; Specht, C.; Lügering, A.; Brzoska, I.; Luger, T. A.; Domschke, W.; Kucharzik, T.
October 2006
Gut;Oct2006, Vol. 55 Issue 10, p1415
Academic Journal
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.


Related Articles

  • Anti-inflammatory properties of the µ opioid receptor support its use in the treatment of colon inflammation. Philippe, David; Dubuquoy, Laurent; Groux, Herve; Brun, Valerie; Tran Van Chuoi-Mariot, Myriam; Gaveriaux-Ruff, Claire; Colombel, Jean-Frederic; Kieffer, Brigite L.; Desreumaux, Pierre // Journal of Clinical Investigation;5/1/2003, Vol. 111 Issue 9, p1329 

    Presents information on a study which examined the role of the anti-inflammatory properties of the µ opiod receptor (MOR) in the treatment of colon inflammation. Description of an intestinal anti-inflammatory activity of MOR agonists; Mechanisms for the abrogation of colitis; Discussion on...

  • Meloxicam.  // Reactions Weekly;6/8/2013, Issue 1456, p23 

    The article presents a case study of a 26-year-old woman who developed colitis after being treated with meloxicam.

  • GASTROHEPATIC DISORDERS.  // MPR - Nurse Practitioners' Edition;Fall2014, Vol. 21 Issue 3, p81 

    The article offers information such as the indications, interactions and adverse reactions of various drug for treating gastrohepatic disorders including the aminosalicylate Apriso from Salix and the stool softener Colace from Purdue Products LP and the opioid Lomotil from Pfizer.

  • 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...

  • Oral high dose Beclomethasone dipropionate for treatment of active ulcerative colitis. Di Caro, Simona; Raimondo, Dario; Mangiavillano, Benedetto; Masci, Enzo; Mariani, Alberto; Gasbarrini, Antonio; De Lorenzo, Antonino; Rienzo, Laura Di; Rocca, Ennio La // Gastroenterology Insights;2012, Vol. 4 Issue 2, p28 

    Oral corticosteroids (CS) have been widely used for treatment of ulcerative colitis (UC) at the price of systemic side effects. Role of topically active oral beclomethasone dipropionate (BDP) in clinical practice is still unclear. The aim of this paper is to investigate efficacy and tolerability...

  • Mesalamine.  // AHFS Consumer Medication Information;Oct2016, p1 

    Mesalamine is used to treat ulcerative colitis (a condition in which part or all of the lining of the colon [large intestine] is swollen or worn away). Mesalamine delayed-release tablets and controlled-release capsules may be used to treat ulcerative colitis that affects any part of the colon....

  • ORAL BUDESONIDE FOR LYMPHOCYTIC COLITIS. Van Gossum, André; Schmit, Alain; Peny, Marie-Odile // American Journal of Gastroenterology;Feb1998, Vol. 93 Issue 2, p270 

    Lymphocytic colitis is a rare inflammatory colonic disease of unknown etiology accompanied by watery diarrhea. Diagnosis is based upon pathological examination of colonic biopsies. Treatment essentially involves antiinflammatory agents such as sulfasalazine/5-ASA or corticosteroids if necessary....

  • Collagenous and Lymphocytic Colitis: Subject Review and Therapeutic Alternatives. Zins, Bradley J.; Sandborn, William J.; Tremaine, William J. // American Journal of Gastroenterology;Sep1995, Vol. 90 Issue 9, p1394 

    Objective: To review the published studies on collagenous and lymphocytic (microscopic) colitis with specific emphasis on clinical features, investigational studies, characteristic histology, possible pathogenesis, disease course, and empirical treatment. Design: Comprehensive synopsis of the...

  • NONSTEROIDAL-INDUCED BENIGN STRICTURES OF THE COLON: A CASE REPORT AND REVIEW OF THE LITERATURE. Eis, Michael J.; Watkins, Brad M.; Philip, Abraham; Welling, Richard E. // American Journal of Gastroenterology;Jan1998, Vol. 93 Issue 1, p120 

    Colonic strictures are a rare complication reported to result from chronic use of sustained release formulations of indomethacin and diclofenac. Such strictures often present with associated mucosal ulceration and are thought to result from nonsteroidal antiinflammatory drug-induced alterations...


Read the Article


Sign out of this library

Other Topics