%0 Journal Article
%T Urolithin A suppresses NLRP3 inflammasome activation by inhibiting the generation of reactive oxygen species and prevents monosodium urate crystal-induced peritonitis.
%A Komatsu W
%A Kishi H
%A Uchiyama K
%A Ohhira S
%A Kobashi G
%J Biosci Biotechnol Biochem
%V 88
%N 8
%D 2024 Jul 22
%M 38772744
%F 2.337
%R 10.1093/bbb/zbae068
%X The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1β (IL-1β) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1β, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species (ROS) and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial ROS.