Enhanced host adaptive response prerequisite to prevent relapse during maintenance therapy of IBD (840.11)

Abstract

Oral administration of DSS in drinking water can induce acute and chronic colitis. Mice that developed colitis showed signs of diarrhea and bleeding within 6‐10 days after 3%‐10% DSS, but pathology of colitis and permeability change was not seen up to 4 days of administration, leading to question why intact colon was preserved in spite of damaging DSS. To answer question, we measured sequential changes of host adaptive phase 2 enzyme as well as damaging genes at 2, 6, 12, 24, 48, 72, 120, and 168hr of DSS. COX‐2 expressions were significantly increased after 120hr accordant with NF‐κB activations/IκBα inhibition. HO‐1 increased between 2‐6hr, NQO1 between 12‐24hr, γ‐GCS between 72‐168hr, of which were all associated with significant activations of Nrf2. Next, we challenged COX‐2‐/‐ and Nrf2‐/‐ mice with DSS to compare pathologic conditions. COX‐2‐/‐ mice showed milder colitis than wild‐type littermates, whereas Nrf2‐/‐ mice showed aggravated colitis followed with increased expression of COX‐2, but no expression of NQO1. Since phase 2 enzyme induction to cope with DSS challenge was essential, we administered oligonol, low molecular polyphenol, in recovered mice from previous DSS challenge and found significantly lower rates of relapse than control group (p<0.001). Our experiments signified the potentiating host adaptive response to prevent relapse of IBD under maintenance therapy.