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Updated: Jul 12, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Potential role for ET-2 acting through ETA receptors in experimental colitis in mice
R F Claudino1,2, D F Leite3, A F Bento3
1Department of Pharmacology, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, SC, Brazil. rfclaudino@gmail.com.
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.
Insights
Endothelin A (ETA) receptor antagonism with Atrasentan effectively reduced colitis severity in mouse models. This suggests ETA receptors are a potential therapeutic target for inflammatory bowel diseases.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Inflammatory bowel diseases (IBD) involve complex inflammatory pathways.
- Endothelins and their receptors (ETA and ETB) play roles in inflammation.
Purpose of the Study:
- To investigate the role of endothelin receptors in mouse models of colitis.
- To evaluate the therapeutic potential of ETA and ETB receptor antagonists.
Main Methods:
- Colitis was induced using 2,4,6-trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS).
- Mice were treated with Atrasentan (ETA antagonist), A-192621 (ETB antagonist), or Dexamethasone.
- Inflammatory parameters and receptor mRNA levels were assessed.
Main Results:
- Atrasentan significantly ameliorated TNBS- and DSS-induced colitis, reducing inflammatory markers.
- A-192621 treatment showed no significant effect on colitis parameters.
- ET-1 and ET-2 mRNA levels fluctuated, while ETA and ETB receptor mRNA increased during colitis.
Conclusions:
- ETA receptor antagonism with Atrasentan is effective in reducing colitis severity.
- ETA receptors represent a promising therapeutic target for inflammatory bowel diseases.
