PUBLICATION

Intestinal Upregulation of Melanin-Concentrating Hormone in TNBS-Induced Enterocolitis in Adult Zebrafish

Authors
Geiger, B.M., Gras-Miralles, B., Ziogas, D.C., Karagiannis, A.K., Zhen, A., Fraenkel, P., and Kokkotou, E.
ID
ZDB-PUB-140303-4
Date
2013
Source
PLoS One   8(12): e83194 (Journal)
Registered Authors
Fraenkel, Paula
Keywords
none
MeSH Terms
  • Administration, Rectal
  • Animals
  • Cell Movement
  • Cytokines/genetics
  • Cytokines/metabolism
  • Disease Models, Animal
  • Enterocolitis/chemically induced
  • Enterocolitis/genetics*
  • Enterocolitis/mortality
  • Enterocolitis/pathology
  • Fish Proteins/genetics*
  • Fish Proteins/metabolism
  • Gene Expression Regulation
  • Humans
  • Hypothalamic Hormones/genetics*
  • Hypothalamic Hormones/metabolism
  • Intestines/metabolism*
  • Intestines/microbiology
  • Intestines/pathology
  • Male
  • Melanins/genetics*
  • Melanins/metabolism
  • Microbiota/drug effects
  • Peroxidase/genetics
  • Peroxidase/metabolism
  • Pituitary Hormones/genetics*
  • Pituitary Hormones/metabolism
  • Receptors, Pituitary Hormone/genetics*
  • Receptors, Pituitary Hormone/metabolism
  • Survival Analysis
  • Trinitrobenzenesulfonic Acid
  • Vancomycin/pharmacology
  • Zebrafish
PubMed
24376661 Full text @ PLoS One
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.

Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes