TY - JOUR
T1 - Effect of endothelin-1 on α-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases
AU - Shahar, Iris
AU - Fireman, Elizabeth
AU - Topilsky, Marcel
AU - Grief, Joel
AU - Schwarz, Yehuda
AU - Kivity, Shmuel
AU - Ben-Efraim, Shlomo
AU - Spirer, Zvi
PY - 1999/11/1
Y1 - 1999/11/1
N2 - Endothelin-1 (ET-1) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AM) and fibroblasts recovered from the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis (SA) and from control subjects. We characterized in vitro alveolar fibroblasts of all subjects using monoclonal antibody specific to α-smooth muscle actin (α-SM actin) and human fibroblast marker. We also examined the effect of ET-1 on the fibroblasts' mitogenesis and on their cytoskeletal phenotype. The AM recovered from IPF patients showed increased spontaneous secretion of ET-1 compared with cells from SA and control subjects. The expression of α-SM actin in the fibroblasts from IPF patients was significantly higher than in SA fibroblasts and normal lung fibroblasts. Assessing alveolar fibroblasts purity revealed a negative staining for α-SM actin in all SA and control fibroblasts, while alveolar fibroblasts recovered from IPF were 100% positive for α-SM actin, a reliable differentiation marker of myofibroblastic cells. Exposure of SA alveolar fibroblasts to ET-1 resulted in an increased expression of α-SM actin. Addition of exogenous ET-1 to alveolar fibroblasts culture stimulated DNA synthesis and proliferation in all groups. Moreover, neutralization of ET-1 by monoclonal antibody was shown to decrease 3H-thymidine incorporation in fibroblasts cultured with AM supernatants. These results suggest possible interactions between AM, myofibroblasts and fibroblasts in interstitial lung diseases (ILD). By modulating α-SM actin expression and exertion of the mitogenic effect on alveolar fibroblasts, ET-1 might play an important role in the fibrogenesis of ILD. Copyright (C) 1999 International Society for Immunopharmacology.
AB - Endothelin-1 (ET-1) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AM) and fibroblasts recovered from the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis (SA) and from control subjects. We characterized in vitro alveolar fibroblasts of all subjects using monoclonal antibody specific to α-smooth muscle actin (α-SM actin) and human fibroblast marker. We also examined the effect of ET-1 on the fibroblasts' mitogenesis and on their cytoskeletal phenotype. The AM recovered from IPF patients showed increased spontaneous secretion of ET-1 compared with cells from SA and control subjects. The expression of α-SM actin in the fibroblasts from IPF patients was significantly higher than in SA fibroblasts and normal lung fibroblasts. Assessing alveolar fibroblasts purity revealed a negative staining for α-SM actin in all SA and control fibroblasts, while alveolar fibroblasts recovered from IPF were 100% positive for α-SM actin, a reliable differentiation marker of myofibroblastic cells. Exposure of SA alveolar fibroblasts to ET-1 resulted in an increased expression of α-SM actin. Addition of exogenous ET-1 to alveolar fibroblasts culture stimulated DNA synthesis and proliferation in all groups. Moreover, neutralization of ET-1 by monoclonal antibody was shown to decrease 3H-thymidine incorporation in fibroblasts cultured with AM supernatants. These results suggest possible interactions between AM, myofibroblasts and fibroblasts in interstitial lung diseases (ILD). By modulating α-SM actin expression and exertion of the mitogenic effect on alveolar fibroblasts, ET-1 might play an important role in the fibrogenesis of ILD. Copyright (C) 1999 International Society for Immunopharmacology.
KW - ET-1
KW - Fibroblasts
KW - Interstitial lung diseases
KW - α-Smooth muscle actin
UR - http://www.scopus.com/inward/record.url?scp=0032825924&partnerID=8YFLogxK
U2 - 10.1016/S0192-0561(99)00056-9
DO - 10.1016/S0192-0561(99)00056-9
M3 - Article
C2 - 10576621
AN - SCOPUS:0032825924
SN - 0192-0561
VL - 21
SP - 759
EP - 775
JO - International Journal of Immunopharmacology
JF - International Journal of Immunopharmacology
IS - 11
ER -
