Yu Xianjun, Zhao Qun, Zhang Xixi, Zhang Haiwei, Liu Yongbo, Wu Xiaoxia, Li Ming, Li Xiaoming, Zhang Jingxuan, Ruan Xuzhi, Zhang Haibing
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China.
Oncotarget. 2017 Jun 27;8(40):67300-67314. doi: 10.18632/oncotarget.18619. eCollection 2017 Sep 15.
Celastrol exhibits potential anti-inflammatory activity in a variety of inflammatory diseases, but the mechanism remains poorly understood. Activation of NLRP3 inflammasome is involved in multiple inflammatory diseases. Here, we show that celastrol abolishes the NLRP3 inflammasome activation, inhibits subsequent caspase-1 activation and IL-1β secretion both and . Notably, interruption of ASC oligomerization and autophagy activation are involved in NLRP3 inflammasome inactivation by celastrol. Importantly, results indicate that celastrol attenuates NLRP3 inflammasome-dependent inflammation diseases via autophagy-related pathway. Our results thus reveal celastrol as an inhibitor of NLRP3 inflammasome, implying the potential for clinical use of celastrol in treatment of NLRP3 inflammasome-driven inflammatory diseases.
雷公藤红素在多种炎症性疾病中表现出潜在的抗炎活性，但其机制仍知之甚少。NLRP3炎性小体的激活与多种炎症性疾病有关。在此，我们发现雷公藤红素可消除NLRP3炎性小体的激活，抑制随后的半胱天冬酶-1激活以及白细胞介素-1β的分泌。值得注意的是，ASC寡聚化的中断和自噬激活参与了雷公藤红素对NLRP3炎性小体的失活作用。重要的是，结果表明雷公藤红素通过自噬相关途径减轻了NLRP3炎性小体依赖性炎症疾病。我们的结果因此揭示了雷公藤红素是NLRP3炎性小体的抑制剂，这意味着雷公藤红素在治疗NLRP3炎性小体驱动的炎症性疾病方面具有临床应用潜力。
