Related Experiment Video
Updated: Aug 5, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
[The effects of nuclear factor-kappaB decoy oligonucleotides on dextran sulphate sodium-induced colitis: experiment
Li-guo Wu1, Hua-tian Gan, Yang-qin Ou
1Department of Digestive Diseases, West China Hospital, Chengdu 610041, China.
Objective:
To investigate the effects of nuclear factor-kappaB (NF-kappaB) decoy oligonucleotide (ODN) on dextran sulphate sodium (DSS)-induced colitis.
Methods:
Nine female BABL/C mice underwent infusion of 0.15 ml normal saline into the distant colon and used as controls (Group 1). Twenty-seven female BABL/C mice were made into DSS-induced colitis models and then randomly divided into 3 groups: Group 2 (underwent infusion of 0.15 ml normal saline into the distant colon), Group 3 (infused with NF-kappaB decoy ODN 25 nmol solved in 0.15 ml), and Group 4 (infused with NF-kappaB scrambled decoy ODN 25 nmol solved in 0.15 ml). Disease active index (DAI) was observed every day. Nine days later the mice were killed and their colons were taken out to undergo histological examination. The tumor necrosis factor (TNF)-alpha level of the colon mucosa was measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB expression was determined by immunohistochemical staining. The distribution of NF-kappaB decoy ODN was investigated by confocal laser microscopy.
Results:
(1) The DAI scores, histological scores and TNF-a level in the colon mucosa of Groups 2 - 4 were all significantly higher than those of Group 1 (all P < 0.05). The DAI scores, histological scores and TNF-a level in the colon mucosa of Group 3 were all significantly lower than those of Groups 2 and 4 (all P < 0.01). (2) In the tissue sections NF-kappaB p65 was positive mainly in the nucleus in the 3 DSS-treated groups without significant differences among these 3 groups, and was mainly positive in the cytoplasm in the control group. (3) Confocal laser microscopy showed that NF-kappaB decoy ODN could be ingested efficiently into the mucosa and submucous layer of colon. (4) There were no significant differences in the liver function, kidney function, and blood glucose among all groups.
Conclusion:
NF-kappaB pathway is associated with the pathogenesis of DSS-induced colitis which is very similar to human UC. Blockade of NF-kappaB pathway by NF-kappaB decoy ODN shows protective effect on the mice with DSS-induced colitis.
Insights
Nuclear factor-kappaB (NF-kappaB) decoy oligonucleotide effectively reduced disease activity and inflammation in a mouse model of dextran sulphate sodium (DSS)-induced colitis. This targeted blockade of the NF-kappaB pathway demonstrates a promising therapeutic strategy for colitis.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Context:
- Dextran sulphate sodium (DSS)-induced colitis is a common model for inflammatory bowel disease research.
- The nuclear factor-kappaB (NF-kappaB) signaling pathway plays a crucial role in mediating inflammatory responses in colitis.
- Developing targeted therapies to inhibit key inflammatory pathways is essential for managing inflammatory bowel diseases.
Purpose:
- To evaluate the therapeutic efficacy of NF-kappaB decoy oligonucleotide (ODN) in a DSS-induced colitis mouse model.
- To assess the impact of NF-kappaB pathway blockade on disease activity, colonic histology, and inflammatory markers.
- To investigate the distribution and cellular uptake of NF-kappaB decoy ODN in the colon.
Summary:
- NF-kappaB decoy ODN significantly reduced disease activity index, histological scores, and tumor necrosis factor-alpha levels in DSS-induced colitis mice compared to controls and scrambled ODN.
- Immunohistochemical analysis revealed NF-kappaB p65 translocation to the nucleus in DSS-treated groups, indicating pathway activation.
- Confocal microscopy confirmed efficient uptake of NF-kappaB decoy ODN into the colonic mucosa and submucosa, suggesting effective delivery.
Impact:
- The findings suggest that NF-kappaB decoy ODN possesses a protective effect against DSS-induced colitis, highlighting its potential as a therapeutic agent.
- This study reinforces the critical role of the NF-kappaB pathway in the pathogenesis of colitis, similar to human ulcerative colitis (UC).
- Targeting the NF-kappaB pathway offers a promising strategy for developing novel treatments for inflammatory bowel diseases.
