PT - JOURNAL ARTICLE AU - Birnhuber, Anna AU - Crnkovic, Slaven AU - Biasin, Valentina AU - Marsh, Leigh M. AU - Odler, Balazs AU - Sahu-Osen, Anita AU - stcher - 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，AID - 10.1183/13993003.00154-2019 DP -2019 9月01日TA -欧洲呼吸杂志PG - 1900154 VI - 54 IP - 3 4099 - //www.qdcxjkg.com/content/54/3/1900154.short 4100 - //www.qdcxjkg.com/content/54/3/1900154.full SO - Eur Respir J2019 9月01日;54 AB -白细胞介素(IL)-1细胞因子家族与系统性硬化症(SSc)和肺受累密切相关，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SSc小鼠模型肺血管和间质重塑中的作用。IL-1α和IL-1β定位于SSc患者的肺部和SSc的fos相关抗原-2 (Fra-2)转基因(TG)小鼠模型。在接受或不接受IL-1受体拮抗剂anakinra (25 mg·kg−1·天−1)治疗8周的fr -2 TG小鼠中测量肺功能、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)和实质成纤维细胞的直接作用。fr -2 TG小鼠肺部胶原沉积增加，肺功能受限，伴随肺动脉高压的血管肌肉化增强，这与SSc患者的变化相似。fr -2 TG小鼠和SSc患者IL-1α和IL-1β的免疫反应性增加。IL-1刺激通过不同的信号通路减少PASMCs和实质成纤维细胞中的胶原蛋白表达。在fr -2 TG中阻断IL-1信号通路会加重肺纤维化和限制，增强t辅助细胞2型(Th2)炎症，并增加促纤维化或激活巨噬细胞的数量。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