title: Melanin-concentrating hormone as a mediator of intestinal inflammation.
abstract: Melanin-concentrating hormone (MCH) is expressed primarily in the hypothalamus and has a positive impact on feeding behavior and energy balance. Although MCH is expressed in the gastrointestinal tract, its role in this system remains elusive. We demonstrate that, compared to wild type, mice genetically deficient in MCH had substantially reduced local inflammatory responses in a mouse model of experimental colitis induced by intracolonic administration of 2,4,6 trinitrobenzene sulfonic acid (TNBS). Likewise, mice receiving treatments with an anti-MCH antibody, either prophylactically or after the establishment of colitis, developed attenuated TNBS-associated colonic inflammation and survived longer. Consistent with a potential role of MCH in intestinal pathology, we detected increased colonic expression of MCH and its receptor in patients with inflammatory bowel disease. Moreover, we found that human colonic epithelial cells express functional MCH receptors, the activation of which induces IL-8 expression. Taken together, these results clearly implicate MCH in inflammatory processes in the intestine and perhaps elsewhere.
authors.affiliation: Gastrointestinal Neuropeptide Center and Center for Inflammatory Bowel Disease, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Efi
authors.initials: E
authors.lastname: Kokkotou
authors.forename: Alan C
authors.initials: AC
authors.lastname: Moss
authors.forename: Daniel
authors.initials: D
authors.lastname: Torres
authors.forename: Iordanes
authors.initials: I
authors.lastname: Karagiannides
authors.forename: Adam
authors.initials: A
authors.lastname: Cheifetz
authors.forename: Sumei
authors.initials: S
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: O'Brien
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Maratos-Flier
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
mesh_terms: D000818:Animals; D003092:Colitis / Q000473:pathology; D003106:Colon / Q000378:metabolism; D017615:Enteric Nervous System / Q000473:pathology; D006801:Humans; D007028:Hypothalamic Hormones / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology; D008297:Male; D008543:Melanins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000737:chemistry; D010907:Pituitary Hormones / Q000502:physiology*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
chemical_list: D007028:Hypothalamic Hormones; D016209:Interleukin-8; D008543:Melanins; D009479:Neuropeptides; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D014302:Trinitrobenzenesulfonic Acid