Search in the Abstract Database

Abstracts Search 2014

* = Presenting author

P076. Enhanced host adaptive response prerequisite to prevent relapse during maintenance therapy of IBD

K.B. Hahm, E.H. Kim, P.W. Park, CHA University, Gastroenterology, Seongnam, South Korea

Background

Oral administration of 40,000 molecular weight dextran sulfate sodium (DSS) in drinking water can induce not only acute, but also chronic colitis, showing extensive injury with complete crypt depletion (mainly basal crypt). Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding, and weight loss within 6–10 days after ingesting 3%-10% DSS. However, overt pathological evidence of colitis was not seen up to 4 days of administration and even permeability change also occurred after 3 days of DSS, leading to question why intact colon was preserved in spite of damaging DSS administrations.

Methods

To answer this question, we measured sequential changes of host adaptive phase 2 enzyme as well as damaging genes 2, 6, 12, 24, 48, 72, 120, and 168 hr of DSS in ICR mice as well as COX-2 knock out and Nrf2 KO mice, respectively (n = 8).

Results

As expected, COX-2 expressions were significantly increased after 120 hr, peak levels at 168 hr in accordant with NF-κB activations/IκBα inhibition. Simultaneous trace of HO-1, NQO1, γ-GCS, and MnSOD showed that HO-1 increased between 2–6hr, NQO1 between 12–24hr, γ-GCS between 72–168, but no change in SOD expression, of which were all associated with significant activations of Nrf2. Based on these in vivo findings, we challenged COX-2−/− and Nrf2−/− mice as well as wild-type littermates with 2.5% DSS compared pathologic conditions and responsible gene expressions. COX-2−/− mice showed milder colitis than wild-type littermates, whereas Nrf2−/− mice showed aggravated colitis followed with extensively increased expression of COX-2, but no expression of NQO1. Supported with these results that intervening of phase 2 enzyme induction to cope with DSS challenge, we administered oligonol, low molecular polyphenol known to induce phase 2 enzyme, in recovered mice from previous DSS challenge as IBD relapse animal model and found significantly lower rates of relapse were seen compared to control group (p < 0.001).

Conclusion

Our experiments signified the potentiating host adaptive response to prevent relapse of IBD under maintenance therapy.