TY -的T1 - NLRP3 inflammasome通路被激活在结节病和参与肉芽肿形成JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00119 -2019欧元SP - 1900119 AU Huppertz鳌,贼鸥Benedikt盟——Wieczorek Grazyna AU -恩格尔哈德,佩吉盟——奥利弗,Stephen J . AU - Bauernfeind Franz-Georg盟——Littlewood-Evans阿曼达盟——Welte Tobias盟——霍农Veit盟——Prasse Antje Y1 - 2020/01/01 UR - //www.qdcxjkg.com/content/early/2020/01/03/13993003.00119 - 2019. -抽象N2 -结节病是一种疾病的特点是肉芽肿形成。有一个未满足的需要新的治疗策略超出皮质类固醇。先天免疫细胞的NLRP3 inflammasome途径表达和感知危险信号引起炎症IL-1β,最近已成为制药靶点。这促使我们测试的角色NLRP3 inflammasome和肉芽肿形成IL-1β通路和结节病。19肉质的患者和19名健康志愿者(高压)加入了这个试点研究。NLRP3 inflammasome活动以BAL-cells和肺和皮肤活检使用免疫组织化学、免疫印迹,rt - pcr和ELISA。在体内实验中我们使用了海藻糖6、6 dimycolate (TDM)肉芽肿小鼠模型和评估肺肉芽肿负担mir - 223 KO和NLRP3 KO小鼠以及MCC950和anti-IL-1β抗体疗法的治疗效果。我们发现强upregulation NLRP3 inflammasome通路,就是表达激活NLRP3 inflammasome组件,包括裂解caspase-1 IL-1β肺肉芽肿,并增加IL-1β释放BAL-cells肉质的患者相比,高压(p = 0.006)。mir - 223的mRNA水平微RNA表达下调NLRP3,是减少和NLRP3 mRNA相应地增加肺泡巨噬细胞结节患者(术中,0.005)。NLRP3 KO小鼠显示下降和mir - 223 KO小鼠肉芽肿的形成与野生型相比增加。药理干预使用NLRP3通路抑制剂MCC950或anti-IL-1β抗体导致降低肉芽肿形成(术中,0.02)。In conclusion, our data provide evidence of upregulated inflammasome and IL-1β pathway activation in sarcoidosis and suggest both as valid therapeutic targets.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Huppertz reports other from Novartis Pharma AG, during the conduct of the study; other from Novartis Pharma AG, outside the submitted work.Conflict of interest: Dr. Jäger has nothing to disclose.Conflict of interest: Dr. Wieczorek reports other from Novartis Pharma AG, during the conduct of the study; other from Novartis Pharma AG, outside the submitted work.Conflict of interest: Dr. Engelhard has nothing to disclose.Conflict of interest: Dr. Oliver reports other from Novartis Pharma AG, during the conduct of the study; other from Novartis Pharma AG, outside the submitted work.Conflict of interest: Dr. Bauernfeind has nothing to disclose.Conflict of interest: Dr. Littlewood-Evans reports other from Novartis Pharma AG, during the conduct of the study; other from Novartis Pharma AG, outside the submitted work.Conflict of interest: Dr. Welte reports grants from Novartis, during the conduct of the study; personal fees from Novartis, outside the submitted work.Conflict of interest: Dr. Hornung has nothing to disclose.Conflict of interest: Dr. Prasse reports grants from Novartis Research Grant, during the conduct of the study; grants and personal fees from Boehringer Ingelheim, personal fees from Roche, personal fees from Novartis, personal fees from Sanofi Aventis, grants and personal fees from Astra Zeneca, outside the submitted work. ER -