title: Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish.
abstract: BACKGROUND
  Melanin-concentrating hormone (MCH), an evolutionarily conserved appetite-regulating neuropeptide, has been recently implicated in the pathogenesis of inflammatory bowel disease (IBD). Expression of MCH is upregulated in inflamed intestinal mucosa in humans with colitis and MCH-deficient mice treated with trinitrobenzene-sulfonic acid (TNBS) develop an attenuated form of colitis compared to wild type animals. Zebrafish have emerged as a new animal model of IBD, although the majority of the reported studies concern zebrafish larvae. Regulation MCH expression in the adult zebrafish intestine remains unknown.
  
  
  METHODS
  In the present study we induced enterocolitis in adult zebrafish by intrarectal administration of TNBS. Follow-up included survival analysis, histological assessment of changes in intestinal architecture, and assessment of intestinal infiltration by myeloperoxidase positive cells and cytokine transcript levels.
  
  
  RESULTS
  Treatment with TNBS dose-dependently reduced fish survival. This response required the presence of an intact microbiome, since fish pre-treated with vancomycin developed less severe enterocolitis. At 6 hours post-challenge, we detected a significant influx of myeloperoxidase positive cells in the intestine and upregulation of both proinflammatory and anti-inflammatory cytokines. Most importantly, and in analogy to human IBD and TNBS-induced mouse experimental colitis, we found increased intestinal expression of MCH and its receptor in TNBS-treated zebrafish.
  
  
  CONCLUSIONS
  Taken together these findings not only establish a model of chemically-induced experimental enterocolitis in adult zebrafish, but point to effects of MCH in intestinal inflammation that are conserved across species.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Geiger
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gras-Miralles
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Dimitrios C
authors.initials: DC
authors.lastname: Ziogas
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Apostolos K A
authors.initials: AK
authors.lastname: Karagiannis
authors.affiliation: Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Aileen
authors.initials: A
authors.lastname: Zhen
authors.affiliation: Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Paula
authors.initials: P
authors.lastname: Fraenkel
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Efi
authors.initials: E
authors.lastname: Kokkotou
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004760:Enterocolitis / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007028:Hypothalamic Hormones / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D008297:Male; D008543:Melanins / Q000235:genetics* / Q000378:metabolism; D064307:Microbiota / Q000187:drug effects; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D010907:Pituitary Hormones / Q000235:genetics* / Q000378:metabolism; D011979:Receptors, Pituitary Hormone / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014302:Trinitrobenzenesulfonic Acid; D014640:Vancomycin / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D016207:Cytokines; D029941:Fish Proteins; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone; D014640:Vancomycin; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase