RT期刊文章SR电子T1 NLRP3炎性途径在结节病中激活，并参与肉芽瘤形成JF欧洲呼吸系统杂志JO EUR RESSIR J FD欧洲呼吸学会SP 1900119 DO 10.1183/13993003.003.003.003.003.003.00119-2019 a1 huppertz，a1 huppertz，huppertz，huppertz，hupper188bet官网地址tz，huppertz，huppertz，cistine a1 jucke a1 jounededede nedededikekt，Grazyna A1 Engelhard，Peggy A1 Oliver，Stephen J. A1 Bauernfeind，Franz-Georg A1 Littlewood-Evans，Amanda A1 Welte，Tobias A1 Hornung，Veit A1 Prasse，Antje yr 2020 ul 2020 ul //www.qdcxjkg.com//erj.erjournals.com/content/早期/2020/01/03/13993003.00119-2019.ABSTRACT AB结节病是一种以肉芽肿形成为特征的疾病。除皮质类固醇外，还需要对新的治疗策略进行未满足的需求。NLRP3炎性体途径在先天免疫细胞中表达，并感觉到引起炎症性IL-1β的危险信号，最近已成为可毒的靶标。这促使我们测试了NLRP3炎性体和IL-1β途径在肉芽瘤形成和结节病中的作用。招募了九十年的肉结杆菌患者和19名健康志愿者（HV）。使用免疫组织化学，Western印迹，RT-PCR和ELISA在BAL细胞，肺和皮肤活检中测量NLRP3炎性体活性。对于体内实验，我们使用了海藻糖6,6二酸（TDM） - 肉芽肿小鼠模型，并评估了miR-223 KO和NLRP3 KO小鼠中的肺肉芽肿负担，以及MCC950和抗IL-1β抗体疗法的治疗作用。我们发现NLRP3炎性体途径的强烈上调，通过激活的NLRP3炎性体成分的表达来证明，包括肺肉芽肿中裂解的caspase-1和IL-1β，与HV相比，从肺部肉芽肿中裂解了Bal细胞的IL-1β释放增加（P= 0.006）。miRNA水平的miRNA水平（一种下调NLRP3的微RNA）降低，NLRP3 mRNA在结节型患者的肺泡巨噬细胞中相应增加（p <0.005）。与野生型相比，NLRP3 KO小鼠显示出降低，而miR-223 KO小鼠的肉芽肿形成增加。 Pharmacological interference using NLRP3 pathway inhibitor MCC950 or an anti-IL-1β antibody resulted in reduced granuloma formation (p<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.