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Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish.

AbstractBACKGROUND:
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.
AuthorsBrenda M Geiger, Beatriz Gras-Miralles, Dimitrios C Ziogas, Apostolos K A Karagiannis, Aileen Zhen, Paula Fraenkel, Efi Kokkotou
JournalPloS one (PLoS One) Vol. 8 Issue 12 Pg. e83194 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID24376661 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Cytokines
  • Fish Proteins
  • Hypothalamic Hormones
  • Melanins
  • Pituitary Hormones
  • Receptors, Pituitary Hormone
  • melanin-concentrating hormone receptor
  • melanin-concentrating hormone
  • Vancomycin
  • Trinitrobenzenesulfonic Acid
  • Peroxidase
Topics
  • Administration, Rectal
  • Animals
  • Cell Movement
  • Cytokines (genetics, metabolism)
  • Disease Models, Animal
  • Enterocolitis (chemically induced, genetics, mortality, pathology)
  • Fish Proteins (genetics, metabolism)
  • Gene Expression Regulation
  • Humans
  • Hypothalamic Hormones (genetics, metabolism)
  • Intestinal Mucosa (metabolism)
  • Intestines (microbiology, pathology)
  • Male
  • Melanins (genetics, metabolism)
  • Microbiota (drug effects)
  • Peroxidase (genetics, metabolism)
  • Pituitary Hormones (genetics, metabolism)
  • Receptors, Pituitary Hormone (genetics, metabolism)
  • Survival Analysis
  • Trinitrobenzenesulfonic Acid
  • Vancomycin (pharmacology)
  • Zebrafish

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