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Updated: Mar 14, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Blockade of the renin-angiotensin system prevents acute and immunologically relevant colitis in murine models
Manabu Okawada1,2, Michael W Wilson3, Scott D Larsen3
1Section of Pediatric Surgery, Department of Surgery, The University of Michigan Medical School, Mott Children's Hospital, F3970, Ann Arbor, MI, 48109-0245, USA. manabu-o@juntendo.ac.jp.
Background:
Blockade of the renin-angiotensin system (RAS) has been shown to alleviate inflammatory processes in the gastrointestinal tract. The aim of this study was to determine if blockade of the RAS would be effective in an immunologically relevant colitis model, and to compare outcome with an acute colitis model.
Methods:
A losartan analog, CCG-203025 (C23H26ClN3O5S) containing a highly polar sulfonic acid moiety that we expected would allow localized mucosal antagonism with minimal systemic absorption was selected as an angiotensin II type 1a receptor antagonist (AT1aR-A). Two colitis models were studied: (1) Acute colitis was induced in 8- to 10-week-old C57BL/6J mice by 2.5 % dextran sodium sulfate (DSS, in drinking water) for 7 days. (2) IL10-/-colitis Piroxicam (200 ppm) was administered orally in feed to 5-week-old IL-10-/-mice (C57BL/6J background) for 14 days followed by enalaprilat (ACE-I), CCG-203025 or PBS administered transanally for 14 days.
Results:
In the DSS model, weight loss and histologic score for CCG-203025 were better than with placebo. In the IL10-/-model, ACE-I suppressed histologic damage better than CCG-203025. Both ACE-I and CCG-203025 reduced pro-inflammatory cytokines and chemokines.
Conclusions:
This study demonstrated the therapeutic efficacy of both ACE-I and AT1aR-A for preventing the development of both acute and immunologically relevant colitis.
Insights
Blockade of the renin-angiotensin system (RAS) effectively treats colitis. Both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1a receptor antagonists (AT1aR-A) showed therapeutic benefits in acute and immunologically relevant colitis models.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) plays a role in gastrointestinal inflammation.
- Investigating RAS blockade for colitis treatment is crucial for developing new therapies.
Purpose of the Study:
- To evaluate the efficacy of RAS blockade in acute and immunologically relevant colitis models.
- To compare the effects of an angiotensin II type 1a receptor antagonist (AT1aR-A) with an angiotensin-converting enzyme inhibitor (ACE-I).
Main Methods:
- Two mouse models of colitis were used: dextran sodium sulfate (DSS)-induced acute colitis and IL-10 knockout (IL10-/-) colitis.
- Mice were treated with an AT1aR-A (CCG-203025), an ACE-I (enalaprilat), or placebo.
Main Results:
- CCG-203025 improved outcomes in the DSS-induced colitis model compared to placebo.
- Both ACE-I and CCG-203025 reduced pro-inflammatory cytokines and chemokines in the IL10-/- model.
- ACE-I demonstrated superior suppression of histologic damage in the IL10-/- model compared to CCG-203025.
Conclusions:
- Both ACE-I and AT1aR-A exhibit therapeutic efficacy in preventing colitis development.
- RAS blockade represents a promising strategy for managing both acute and immunologically relevant colitis.
