Urolithin A suppresses NLRP3 inflammasome activation by inhibiting the generation of reactive oxygen species and prevents monosodium urate crystal-induced peritonitis.
Wataru Komatsu, Hisashi Kishi, Koji Uchiyama, Shuji Ohhira, Gen Kobashi
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引用次数: 0
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.
尿石素 A 可通过抑制活性氧的生成来抑制 NLRP3 炎症小体的激活,并可预防单钠尿酸盐晶体诱发的腹膜炎。
NOD 样受体家族含 pyrin 结构域的蛋白 3(NLRP3)炎性体会触发白细胞介素-1β(IL-1β)的成熟,并与各种炎症性疾病的发病机制有关。据报道,鞣花酸的肠道微生物代谢产物尿石素 A 在体外和体内都有抗炎作用。然而,尿石素 A 是否能抑制 NLRP3 炎性体的激活尚不清楚。在这项研究中,尿石素 A 可抑制 NLRP3 炎症小体激动剂诱导的 caspase-1 的裂解、IL-1β 的成熟以及脂多糖激发的小鼠骨髓巨噬细胞中热凋亡的激活。尿胆素 A 减少了细胞内和线粒体中活性氧的生成,并限制了硫氧还蛋白与 NLRP3 的相互作用,从而减轻了 NLRP3 炎性体的激活。服用尿胆素 A 可预防单钠尿酸盐诱发的小鼠腹膜炎。总之,这些研究结果表明,尿胆素 A 至少部分抑制了细胞内和线粒体活性氧的生成,从而抑制了 NLRP3 炎症小体的激活。
期刊介绍:
Bioscience, Biotechnology, and Biochemistry publishes high-quality papers providing chemical and biological analyses of vital phenomena exhibited by animals, plants, and microorganisms, the chemical structures and functions of their products, and related matters. The Journal plays a major role in communicating to a global audience outstanding basic and applied research in all fields subsumed by the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA).