Regulation of the inflammasome adaptor ASC mediated singling and arthritis diseases
作者单位：Institute of Ageing Research Hangzhou Normal University School of Medicine
会议名称：《第十届全国免疫学学术大会》
会议日期：2015年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：inflammasome
摘 要：Rheumatoid arthritis is a chronic autoinflammatory disease. Interlenkin-1b(IL-1b) is a key factor of cartilage destruction in rheumatic disease, but the regulation of IL-1b in rheumatoid arthritis is limited by the absence of suitable mouse models of the disease. Here, we show that ASC, a component of the inflammasome complex promotes IL-1b secretion and modulates synovial inflammation in the K/Bx N serum transfer induced arthritis models. That it crucially relies on the ASC inflammasome and IL-1b receptor signaling, but that regulation is unknown. In the macrophages, when we lacking PLZF has decreased the protein expression level of the inflammasome adaptor ASC, in contrast the pro IL-1b is not altered. As a result, PLZF deficiency in the macrophages significantly reduced ASC inflammasome-mediated caspase-1 activation, pyroptosis and IL-1 b secretion by number of NLRP3 stimuli. Importantly, decreased ASC inflammasome activation limited the pathology of rheumatoid arthritis was found in the PLZF deficiency mice. These results reveal PLZF as a novel regulator of ASC inflammasome mediated capase-1 activation and IL-1b secretion, and subsequently promote rheumatoid arthritis associated inflammasome disease and cartilage destruction.