Dosreis G A, Borges Valeria M, Zin W A
Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21949-900, Brazil.
J Cell Mol Med. 2004 Jul-Sep;8(3):285-93. doi: 10.1111/j.1582-4934.2004.tb00318.x.
Following inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas-Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL-1 beta and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas-FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung diseases.
肺部发生炎症和损伤后,上皮细胞前体的丧失可能决定组织再生与纤维化之间的平衡。本综述讨论了促凋亡的Fas - Fas配体(FasL)信号在肺部炎症、损伤和纤维化中起核心作用的证据。FasL信号在上皮细胞和肺泡巨噬细胞中诱导炎性凋亡,同时释放白细胞介素-1β和趋化因子,导致中性粒细胞浸润。FasL信号在急性肺损伤、特发性肺纤维化和矽肺模型中起关键作用;阻断Fas - FasL相互作用可预防或减轻肺部炎症和纤维化。对患者的血清学和免疫组织化学研究支持Fas和FasL分子在炎性肺病中起主要致病作用。确定FasL的致病作用有助于发现针对目前无法治疗的炎性肺病更有效的治疗方法。