TY -的T1 - il - 1受体封锁的倾斜向Th2炎症在小鼠模型的系统性硬化症JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00154 -2019欧元六世- 54 - 3 SP - 1900154 AU Birnhuber安娜盟——Crnkovic抢盟——Biasin瓦伦蒂娜AU -马什,李·m . AU -光延迟线,Balazs AU - Sahu-Osen,Anita AU - Stacher-Priehse, Elvira AU - Brcic, Luka AU - Schneider, Frank AU - Cikes, Nada AU - Ghanim, Bahil AU - Klepetko, Walter AU - Graninger, Winfried AU - Allanore, Yannick AU - Eferl, Robert AU - Olschewski, Andrea AU - Olschewski, Horst AU - Kwapiszewska，Grazyna Y1 - 2019/09/01 UR - //www.qdcxjkg.com/content/54/3/1900154.abstract N2 -白细胞介素(IL)-1家族细胞因子与系统性硬化症(SSc)和肺受受性密切相关，但其分子机制尚不清楚。本研究的目的是评估IL-1α和IL-1β在小鼠SSc模型肺血管和间质重构中的作用。IL-1α和IL-1β在SSc患者肺部和fos相关抗原-2 (fra2)转基因(TG)小鼠模型中定位。在使用或不使用IL-1受体拮抗剂阿纳金拉(25mg·kg−1·day−1)治疗8周后，测量fra2 TG小鼠的肺功能、血流动力学参数和肺部炎症。研究了IL-1对肺动脉平滑肌细胞(PASMCs)和肺实质成纤维细胞的直接作用。fra2 TG小鼠表现出肺胶原沉积增加，限制性肺功能增强，血管肌肉化增强，伴肺动脉高压，让人联想到SSc患者的变化。IL-1α和IL-1β的免疫反应性在fra2 TG小鼠和SSc患者中升高。IL-1刺激可通过不同的信号通路降低PASMCs和实质成纤维细胞中胶原的表达。在fra2 TG中阻断IL-1信号使肺纤维化恶化，限制，t辅助细胞2型(Th2)炎症增强，促纤维化、交替活化的巨噬细胞数量增加。Our data suggest that blocking IL-1 signalling as currently investigated in several clinical studies might aggravate pulmonary fibrosis in specific patient subsets due to Th2 skewing of immune responses and formation of alternatively activated pro-fibrogenic macrophages.IL-1 dampens collagen production of lung structural cells and balances pro-fibrotic actions of the immune system. Blockade of IL-1 signalling in Fra-2 TG mice worsens lung function by increased Th2 inflammation and collagen production in the lung. http://bit.ly/2IVUGLX ER -