6th Annual BMRP Investigator Meeting - Abstract
Melanin-Concentrating Hormone (MCH) Elicits Proinflammatory Responses in Colonocytes and Adipocytes
Iordanis Karagiannides1, Daniel Espinoza1, Alan Moss1, James Kirkland2, Charalabos Pothoulakis1, Efi Kokkotou1,a
1Gastrointestinal Neuropeptide Center, Beth Israel Deaconess Medical Center and Harvard Medical School (Boston, Massachusetts, U.S.A.); 2Obesity Research Center, Department of Medicine, Genetics and Genomics, Boston University School of Medicine (Massachusetts, U.S.A.)
MCH is a satiety hormone expressed primarily in the hypothalamus. Our recent studies revealed a significant role of MCH in intestinal inflammation, in addition to its role in appetite regulation and energy balance. MCH and its receptor (MCHR1) are upregulated in the affected mucosa of patients with Inflammatory Bowel Disease (IBD) and MCH-deficient mice develop attenuated TNBS-induced colitis. Among the cell types that we found to express MCHR1 in the intestine are colonic epithelial cells and adipocytes. In both cell types, MCHR1 expression is induced by inflammatory stimuli. Treatment of NCM460 non-transformed human colonic epithelial cells with MCH resulted in MAP-kinase, STAT-3 and NF-κappaB activation and transcriptional upregulation of their downstream targets IL-3, IL-5, IL-7, IL-8, IL-12A, MIP-3, MCP-1, MCP-3, CXCL6, CX3CL1 and ICOS. Likewise, MCH treatment of human primary adipocyte cultures of mesenteric origin stimulated IL-8 and MCP-1 expression. Taken together, these results provide a potential mechanism by which MCH contributes to the pathogenesis of Crohn’s disease and its associated “creeping fat”.
aPrincipal Investigator