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• W2158602178 abstract "<b>Background and aims:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 <i>Citrobacter rodentium</i>. 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. <b>Conclusions:</b> 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." @default.
• W2158602178 created "2016-06-24" @default.
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• W2158602178 date "2006-10-01" @default.
• W2158602178 modified "2023-09-25" @default.
• W2158602178 title "Crucial role of the melanocortin receptor MC1R in experimental colitis" @default.
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• W2158602178 doi "https://doi.org/10.1136/gut.2005.083634" @default.
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