Crucial role of the melanocortin receptor MC1R in experimental colitis.
Gut
; 55(10): 1415-22, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-16543288
ABSTRACT
BACKGROUND AND AIMS:
alpha-Melanocyte stimulating hormone (alpha MSH) is known to exert anti-inflammatory effects, for example in murine DSS (dextran sodium sulphate induced) colitis. The anti-inflammatory functions of alpha MSH 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 alpha MSH-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 MC1Re/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 of MC1R in intestinal inflammation. The data suggest a pivotal role of non-haematopoietic cell expressed MC1R in the host's response to pathogenic stimuli.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alfa-MSH
/
Colite
/
Receptor Tipo 1 de Melanocortina
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article