Melanin-concentrating hormone as a mediator of intestinal inflammation.
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.
Kokkotou
Efi
E
Gastrointestinal Neuropeptide Center and Center for Inflammatory Bowel Disease, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Moss
Alan C
AC
Torres
Daniel
D
Karagiannides
Iordanes
I
Cheifetz
Adam
A
Liu
Sumei
S
O'Brien
Michael
M
Maratos-Flier
Eleftheria
E
Pothoulakis
Charalabos
C
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
D007028:Hypothalamic Hormones; D016209:Interleukin-8; D008543:Melanins; D009479:Neuropeptides; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D014302:Trinitrobenzenesulfonic Acid