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.
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Authors | Brenda M Geiger, Beatriz Gras-Miralles, Dimitrios C Ziogas, Apostolos K A Karagiannis, Aileen Zhen, Paula Fraenkel, Efi Kokkotou |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 12
Pg. e83194
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24376661
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Cytokines
- Fish Proteins
- Hypothalamic Hormones
- Melanins
- Pituitary Hormones
- Receptors, Pituitary Hormone
- melanin-concentrating hormone receptor
- melanin-concentrating hormone
- Vancomycin
- Trinitrobenzenesulfonic Acid
- Peroxidase
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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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