Abstract：
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.
摘要：
NOD样受体家族含pyrin结构域的蛋白3（NLRP3）炎性体触发白介素1β（IL-1β）的成熟，并参与各种炎性疾病的发病机理。尿磷脂A,鞣花酸的肠道微生物代谢产物，据报道在体外和体内发挥抗炎作用。然而,尿石素A是否抑制NLRP3炎性体激活尚不清楚.在这项研究中,尿石素A抑制NLRP3炎性体激动剂诱导的caspase-1的裂解，IL-1β的成熟，和激活脂多糖引发的小鼠骨髓源性巨噬细胞的焦亡。尿石素A减少了细胞内和线粒体活性氧的产生，并限制了硫氧还蛋白相互作用蛋白与NLRP3之间的相互作用，从而减弱了NLRP3炎性体的激活。尿石素A给药可预防尿酸单钠诱导的小鼠腹膜炎。总的来说，这些发现表明尿石素A抑制NLRP3炎性体激活，至少部分地,通过抑制细胞内和线粒体活性氧的产生。
