RT期刊文章SR电子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摩根富林明欧洲呼吸杂志乔和J FD欧元欧洲呼吸学会SP 1900154 10.1183/13993003.00154 -2019签证官54是3 A1 Birnhuber,安娜A1 Crnkovic,抢A1 Biasin,瓦伦蒂娜A1沼泽,188bet官网地址Leigh M. A1 Odler, Balazs A1 sahuu - osen, Anita A1 Stacher-Priehse, Elvira A1 Brcic, Luka A1 Schneider, Frank A1 Cikes, Nada A1 Ghanim, Bahil A1 Klepetko, Walter A1 Graninger, Winfried A1 Allanore, Yannick A1 Eferl, Robert A1 Olschewski, Andrea A1 Olschewski, Horst A1 Kwapiszewska，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