Equol inhibits NLRP3 inflammasome activation in macrophages 2257578

Introduction The intestinal microbiome produces a vast number of metabolites. Many of these metabolites have immunomodulatory properties including the ability to inhibit the NOD, LRR, and pyrin-domain containing 3 (NLRP3) inflammasome, an established driver of inflammation in many diseases including gout, psoriasis, and Alzheimer’s disease. Methods Therefore, we developed an enzyme-linked immunosorbent assay (ELISA) based screen to identify metabolites with the potential to inhibit NLRP3 activation. Using this screen, we identified equol, a metabolite of the soy isoflavone daidzein, as a strong candidate. Additional ELISAs and caspase-1 immunoblots further validated that equol inhibits ATP dependent NLRP3 activation in murine bone marrow derived macrophages (BMDMs), evidenced by significantly decreased IL-1β secretion and caspase-1 processing after equol treatment. Results Our work indicates equol’s anti-inflammatory effects are specific to the NLRP3 inflammasome; treatment with equol does not alter the secretion of several other inflammatory cytokines/chemokines (TNFα, IL-6, CXCL1, MIP-1α, RANTES) or activation of the AIM2 or NLRC4 inflammasomes in BMDMs. Conclusion These findings lay a strong foundation for future studies examining the immunomodulatory action of equol in mouse models of NLRP3 driven disease. Funding Source This work was supported by funds from the William F.