Role of F2-Isoprostanes in lung fibrosis

Several studies have shown the involvement of oxidative stress in a number of pulmonary diseases and have reported that F2-isoprostanes (IsoPs), the most reliable markers of oxidative stress, are increased in some lung pathologies. On the basis of the results previously obtained in experimentally induced liver fibrosis, we investigated the possible relevance of IsoPs in the model of bleomycin-induced lung fibrosis. Bleomycin-administration to young rats caused the development of pulmonary fibrosis accompanied by an increase in plasma IsoPs, which was prominent during the first days after treatment. Lung sections from bleomycin-treated rats showed cells expressing alpha-smooth muscle actin (-SMA), the marker of activated myofibroblast phenotype. In addition, freshly isolated lung fibroblasts treated with IsoPs showed significative increase of alpha-SMA expression as compared to control, indicating that IsoPs can readily activate fibroblasts to myofibroblasts. Moreover, the addition of IsoPs to lung fibroblasts from normal animals resulted in an increase in cell proliferation and collagen synthesis. Immunocytochemistry analysis revealed the presence of TxA2 receptor (TP) both on fibroblasts and myofibroblasts suggesting that the effects of IsoPs may be mediated by TP. Our data suggest that IsoPs could play an important role in the onset of the alterations eventually leading to lung fibrosis.