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Inflammation Research
Erschienen in: Inflammation Research 2/2017

24.10.2016 | Original Research Paper

Potential role for ET-2 acting through ETA receptors in experimental colitis in mice

verfasst von: R. F. Claudino, D. F. Leite, A. F. Bento, J. G. Chichorro, J. B. Calixto, G. A. Rae

Erschienen in: Inflammation Research | Ausgabe 2/2017

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Abstract

Objective and design

This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETB receptors in mouse models of colitis.

Materials and methods

Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ETA receptor antagonist, 10 mg/kg), A-192621 (ETB receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors.

Results

Atrasentan treatment ameliorates TNBS- and DSS-induced colitis. In the TNBS model was observed reduction in macroscopic and microscopic score, colon weight, neutrophil influx, IL-1β, MIP-2 and keratinocyte chemoattractant (KC) levels, inhibition of adhesion molecules expression and restoration of IL-10 levels. However, A192621 treatment did not modify any parameter. ET-1 and ET-2 mRNA was decreased 24 h, but ET-2 mRNA was markedly increased at 48 h after TNBS. ET-2 was able to potentiate LPS-induced KC production in vitro. ETA and ETB receptors mRNA were increased at 24, 48 and 72 h after colitis induction.

Conclusions

Atrasentan treatment was effective in reducing the severity of colitis in DSS- and TNBS-treated mice, suggesting that ETA receptors might be a potential target for inflammatory bowel diseases.
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Metadaten
Titel
Potential role for ET-2 acting through ETA receptors in experimental colitis in mice
verfasst von
R. F. Claudino
D. F. Leite
A. F. Bento
J. G. Chichorro
J. B. Calixto
G. A. Rae
Publikationsdatum
24.10.2016
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 2/2017
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-016-1001-7

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