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Updated: Jun 18, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
TLR4 monoclonal antibody blockade suppresses dextran-sulfate-sodium-induced colitis in mice
Yi Liu1, Zhijun Zhang, Lei Wang
1Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China. liuyi0205@sina.com
Background And Aim:
Ulcerative colitis (UC) refers to a kind of inflammatory bowel disease, of which the accurate pathogenesis is not yet well understood. Recently, the toll-like receptor 4 (TLR4) and the TLR4 signaling pathway have been proved as playing an important role in the pathogenesis of UC. The objective of this study was to evaluate the effect of TLR4 monoclonal antibody on dextran-sulfate-sodium-induced colitis in a mouse model.
Methods:
We evaluated the effects of the TLR4 monoclonal antibody (TLR4mAb) on the development of dextran-sulfate-sodium-(DSS)-induced colitis. Tissue samples were evaluated by the disease activity index and histopathological score. Meanwhile, the mucosal mRNA expression of cytokines, tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta were analyzed by semiquantitative reverse transcription polymerase chain reaction. The mucosal protein P38-MAPK, c-jun and c-fos expressions of the TLR4-P38MAPK pathway were analyzed using Western blot.
Results:
After the treatment with TLR4mAb against DSS-induced colitis, the bodyweight was significantly increased and both disease activity index and histopathological score were decreased significantly. Furthermore, the mucosal expression of messenger RNA of tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta were observed to be 8-15-fold more than the baseline, whereas the mucosal expressions of P38MAPK and c-jun were found to be decreased.
Conclusion:
Blocking TLR4 by TLR4mAb can prevent the development of DSS-induced colitis through the TLR4-P38MAPK-c-jun pathway.
Insights
Blocking toll-like receptor 4 (TLR4) with a monoclonal antibody (TLR4mAb) significantly reduced disease severity in a mouse model of ulcerative colitis. This suggests TLR4 is a key therapeutic target for inflammatory bowel disease.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Ulcerative colitis (UC) is an inflammatory bowel disease with incompletely understood pathogenesis.
- Toll-like receptor 4 (TLR4) and its signaling pathway are implicated in UC development.
- Targeting TLR4 may offer a therapeutic strategy for UC.
Purpose of the Study:
- To evaluate the therapeutic effect of a TLR4 monoclonal antibody (TLR4mAb) in a mouse model of dextran-sulfate-sodium (DSS)-induced colitis.
- To investigate the impact of TLR4 blockade on key inflammatory markers and signaling pathways involved in colitis.
Main Methods:
- Induction of colitis in mice using DSS.
- Administration of TLR4mAb to treat DSS-induced colitis.
- Assessment of disease activity, histopathology, cytokine mRNA expression (TNF-α, IFN-γ, IL-1β), and Western blot analysis of P38-MAPK, c-jun, and c-fos protein expression.
Main Results:
- TLR4mAb treatment significantly increased body weight and decreased disease activity index and histopathological scores.
- Mucosal expression of TNF-α, IFN-γ, and IL-1β mRNA increased 8-15 fold compared to baseline.
- Mucosal protein expression of P38-MAPK and c-jun was decreased.
Conclusions:
- Blocking TLR4 with TLR4mAb effectively ameliorates DSS-induced colitis in mice.
- The TLR4-P38MAPK-c-jun pathway is crucial in the pathogenesis of DSS-induced colitis.
- TLR4mAb represents a potential therapeutic agent for ulcerative colitis by modulating this pathway.
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