Ty-jour t1 - 吸烟者外周血免疫细胞蛋白酶激活和copd患者的激活 - 治疗JF - 欧洲呼吸杂志Jo - Eur Respir J Do - 10.1183 / 13993003 - 2101798-2021 SP - 2101798 Au - Kammerl，Ilona E. Au- Hardy，Sophie Au - Flexeder，Claudia Au - Urmann，Andrea Au - Peierl，Julia Au - Wang，Yuqin Au - Vosyka，Oliver Au - Frankenberger，Marion Au - Milger，Katrin Au - Behr，Jürgen·奥尔克，安德烈奥- Merl-Pham，Juliane Au - Hauck，Stefanie M. Au - Pilette，Charles Au - Schulz，Holger Au - Meiners，Silke Y1 - 2021/01/01 UR - //www.qdcxjkg.com/content/early/2021/07/21/13993003.01798-2021.abstract N2 - Immune cells contain a specialised type of proteasome, i.e. the immunoproteasome, which is required for intracellular protein degradation. Immunoproteasomes are key regulators of immune cell differentiation, inflammatory activation and autoimmunity. Immunoproteasome function in peripheral immune cells might be altered by smoking and in COPD thereby affecting immune cell responses.We here analysed the expression and activity of proteasome complexes in peripheral blood mononuclear cells (PBMC) isolated from healthy male young smokers as well as from patients with severe COPD and compared them to matching controls. Proteasome expression was upregulated in COPD patients as assessed by RT-qPCR and mass spectrometry-based proteomics analysis. Proteasome activity was quantified using activity-based probes and native gel analysis. We observed distinct activation of immunoproteasomes in the peripheral blood cells of young male smokers and severely ill COPD patients. Native gel analysis and linear regression modeling confirmed robust activation and elevated assembly of 20S proteasomes, which correlated significantly with reduced lung function parameters in COPD patients. The immunoproteasome was distinctly activated in COPD patients upon inflammatory cytokine stimulation of PBMCs in vitro. Inhibition of the immunoproteasome reduced proinflammatory cytokine expression in COPD-derived blood immune cells.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 -