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Updated: Jan 21, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
PAP-1 ameliorates DSS-induced colitis with involvement of NLRP3 inflammasome pathway
Yongyu Mei1, Chen Fang1, Shaozhen Ding1
1Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, The Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China.
Background:
Macrophages are a primary type of innate immune cells activated in colitis. Kv1.3 channel is one of the major potassium channels in macrophages. NLRP3 inflammasome is a downstream molecule of Kv1.3 channel. PAP-1, a specific Kv1.3 channel blocker, has been shown to have immune-regulatory effects.
Objective:
To investigate the effect of PAP-1 on intestinal inflammation in DSS-induced colitis and explore its possible mechanism.
Methods:
C57BL/6 mice were divided into four groups: normal control group, normal+PAP-1 injection group, DSS model group, DSS model+PAP-1 injection group. Experimental colitis was induced by 5% DSS treatment; mice were injected intraperitoneally with PAP-1 from the first day for 7 consecutive days; then all mice were sacrificed, followed by isolation of colon tissue, peritoneal macrophages and spleen macrophages. The anti-inflammatory effects of PAP-1 and the expression levels of Kv1.3, iNOS, pro-IL-1β, IL-1β and NLRP3 inflammasome were measured.
Results:
PAP-1 reduced DSS-induced colonic pathological damage, DAI score, MPO activity and levels of IL-1, IL-6, TNF-a, IL-18. Compared with the DSS model group, the expression of Kv1.3, iNOS, NLRP3, ASC, caspase-1p20, pro-IL-1β and IL-1β in colon were decreased in the DSS-induced colitis mice with PAP-1 injection. PAP-1 also reduced the expression of Kv1.3, iNOS, NLRP3, caspase-1p20 and IL-1β on macrophages in colitis mice.
Conclusion:
PAP-1 had protective effects on DSS-induced colitis, which might be ascribed to the regulation of NLRP3 inflammasome pathway. Therefore, we found that PAP-1 was useful as a therapeutic agent in IBD and suggested a potential important role of PAP-1 in NLRP3 inflammasome-associated diseases.
Insights
PAP-1, a Kv1.3 channel blocker, reduced intestinal inflammation and colonic damage in DSS-induced colitis. This protection is linked to the regulation of the NLRP3 inflammasome pathway, suggesting PAP-1 as a potential therapeutic for IBD.
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- Macrophages are key innate immune cells activated during colitis.
- The Kv1.3 channel and NLRP3 inflammasome are implicated in macrophage activation.
- PAP-1, a Kv1.3 channel blocker, exhibits immune-regulatory properties.
Purpose of the Study:
- To evaluate PAP-1's therapeutic effect on intestinal inflammation in DSS-induced colitis.
- To elucidate the underlying mechanism involving the NLRP3 inflammasome pathway.
Main Methods:
- Experimental colitis was induced in C57BL/6 mice using 5% DSS.
- Mice received daily intraperitoneal injections of PAP-1.
- Colon tissue and macrophages were analyzed for inflammatory markers and protein expression (Kv1.3, iNOS, NLRP3 inflammasome components).
Main Results:
- PAP-1 significantly reduced colonic pathological damage, disease activity, and MPO activity.
- PAP-1 decreased pro-inflammatory cytokines (IL-1, IL-6, TNF-a, IL-18) in DSS-treated mice.
- Expression of Kv1.3, iNOS, and NLRP3 inflammasome components was downregulated by PAP-1 in colon and macrophages.
Conclusions:
- PAP-1 demonstrates protective effects against DSS-induced colitis.
- The mechanism involves the modulation of the NLRP3 inflammasome pathway.
- PAP-1 shows therapeutic potential for inflammatory bowel disease (IBD) and NLRP3 inflammasome-associated conditions.
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