TY -的T1 -激活免疫细胞水解酶在吸烟者和慢性阻塞性肺病患者的外周血-影响治疗JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.01798 -2021欧元SP - 2101798 AU Kammerl Ilona e . AU -哈迪,苏菲AU -弯曲,克劳迪娅AU - Urmann,安德里亚盟——Peierl,茱莉亚盟——王,Yuqin盟——Vosyka奥利弗盟——私生子,马里昂AU - Milger,凯特琳AU - Behr Jurgen AU -科赫,安德里亚盟——Merl-Pham Juliane AU -豪Stefanie m . AU - Pilette查尔斯AU -舒尔茨,Holger盟——Meiners Silke Y1 - 2021/01/01 UR - //www.qdcxjkg.com/content/early/2021/07/21/13993003.01798 - 2021. -抽象N2 -免疫细胞含有一种专门的蛋白酶体,即immunoproteasome,所需的细胞内蛋白质的降解。Immunoproteasomes免疫的关键调节细胞分化、炎症和自身免疫激活。Immunoproteasome功能外周免疫细胞可能会改变在吸烟和慢性阻塞性肺病从而影响免疫细胞的反应。我们分析了水解酶的表达和活性复合物在外周血单核细胞(PBMC)隔绝年轻健康男性吸烟者以及严重的慢性阻塞性肺病患者,相比他们匹配控制。蛋白酶体表达被RT-qPCR调节在慢性阻塞性肺病患者评估和质量spectrometry-based蛋白质组学分析。蛋白酶体活性量化使用基于活动的调查和本地凝胶分析。我们观察到不同的激活immunoproteasomes外周血细胞的年轻男性吸烟者和重症慢性阻塞性肺病患者。本机凝胶分析和线性回归建模证实健壮的激活和组装20年代水解酶升高,显著相关,降低COPD患者的肺功能参数。immunoproteasome是明显激活炎性细胞因子在慢性阻塞性肺病患者PBMCs体外的刺激。抑制的immunoproteasome COPD-derived血液中促炎细胞因子表达的免疫细胞减少。Given the crucial role of chronic inflammatory signalling and the emerging involvement of autoimmune responses in COPD, therapeutic targeting of the immunoproteasome might represent a novel therapeutic concept for COPD.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. Kammerl has nothing to disclose.Conflict of interest: Dr. Hardy has nothing to disclose.Conflict of interest: C. Flexeder has nothing to disclose.Conflict of interest: A. Urmann has nothing to disclose.Conflict of interest: Dr. Peierl has nothing to disclose.Conflict of interest: Dr. Wang has nothing to disclose.Conflict of interest: Dr. Vosyka has nothing to disclose.Conflict of interest: Dr. Frankenberger has nothing to disclose.Conflict of interest: Dr. Milger reports personal fees from Astrazeneca, BerlinChemie, GSK, Novartis, Sanofi, outside the submitted work; .Conflict of interest: Dr. Behr has nothing to disclose.Conflict of interest: Dr. Koch has nothing to disclose.Conflict of interest: Dr. Merl-Pham has nothing to disclose.Conflict of interest: Dr. Hauck has nothing to disclose.Conflict of interest: Dr. Pilette has nothing to disclose.Conflict of interest: Dr. Schulz has nothing to disclose.Conflict of interest: Dr. Meiners has nothing to disclose. ER -