Presenting Author: Piu Saha
, Research Assistant Professor at Univ. of Toledo Col. of Med. and Life Sci.
Abstract:
One serious extra-intestinal manifestation of Inflammatory Bowel Disease (IBD) is iron deficiency anemia (IDA). The first choice for IDA therapy is oral iron supplementation; yet the rhetoric that IDA can be ‘treated’ with iron is far from accurate, given the high incidence of severe side effects. We herein investigated the extent to which NLRP3 (NOD-like receptor 3) inflammasome could influence iron-induced adverse effects in IBD. Wild-type (WT) and NLRP3-deficient (Nlrp3KO) mice were treated with dextran sodium sulfate (DSS) for 7 days and then oral FeSO4 (Fe2+) was administered for 3 days. Fe2+ augmented colonic inflammation in WT, but not in Nlrp3KO mice. Histological analysis revealed that iron+DSS treated WT colitic mice displayed more inflammation than Nlrp3KO mice. Interestingly, oral administration of β-hydroxybutyrate (BHB, inhibitor of NLRP3) significantly reduced the Fe2+ induced inflammation in WT mice. Next, to evaluate the role of endogenous iron in colitis, we used homeostatic iron regulator protein (HFE)-deficient mice (HfeKO), which were noted to be highly susceptible to IL-10R neutralization-induced colitis. Intriguingly, deficiency of NLRP3 in HfeKO mice (Hfe-Nlrp3-DKO) significantly protected them from IL-10R neutralization-induced colitis. In conclusion, our study demonstrates that excess iron could exacerbate inflammation during IBD and that BHB could be used as a therapeutic to mitigate iron-induced inflammation in IBD.
Blocking of NLRP3 inflammasome activity alleviates iron-induced adverse effects in murine models of colitis
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 01:30 PM to 01:45 PM Room: Room W179