Differential Proliferative Characteristics of Alveolar Fibroblastsin Interstitial Lung Diseases: Regulative Role of IL-1 and PGE2

[摘要] Fibroblasts (Fb) from patients with sarcoidosis (SA) andhypersensitivity pneumonitis (HP) exhibited a lower proliferativecapacity compared with Fb obtained from control (CO) and diffuseinterstitial fibrosis patients (DIF). Proliferation of Fb from SA orlip patients was suppressed by autologous LPS-stimulated alveolarmacrophages (AM) supernatants but not by those from CO patients.Similarly, alveolar macrophages (AM) derived supernatant, obtainedfrom CO, did not suppress the proliferation of SA and HP Fb. AM fromSA and HP patients secreted higher amounts of IL-1α and βcompared with controls and compared with Fb from SA and HP patients.Steady levels of IL-1α and βmRNA were expressed inunstimulated and stimulated cultures. Fb from SA and HP patientscould be stimulated by LPS to secrete significantly higher levels ofPGE2than those detected in supernatants from LPSstimulated Fb of DIF patients. Only the proliferation of Fb from SAand HP patients was sensitive to amounts of IL-1 equivalent to thosedetected in the lung of these diseases. As SA and HP are twodiseases where irreversible deterioration occurs in only 20%of the patients, we hypothesize that mediators in the lung maymodulate Fb proliferation. IL-1 of AM origin and PGE2ofFb origin secreted at high levels, may be candidates for thissuppression because it was abrogated by anti IL-1β and indomethacin.

[学科分类] 生理学与病理学