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Interferon-β Inhibits Bleomycin-Induced Lung Fibrosis by Decreasing Transforming Growth Factor-β and Thrombospondin

2004; American Thoracic Society; Volume: 32; Issue: 2 Linguagem: Inglês

10.1165/rcmb.2003-0374oc

1535-4989

Arata Azuma, Ying Ji Li, Shinji Abe, Jiro Usuki, Kuniko Matsuda, Satoshi Henmi, Yasushi Miyauchi, Kohei Ueda, Akiko Izawa, Saburo Sone, Shu Hashimoto, Shoji Kudoh,

Pulmonary Hypertension Research and Treatments

Pulmonary fibrosis is the result of abnormal processes of repair that occur after lung injury. Transforming growth factor (TGF)-beta is a key molecule in the progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta did not improve survival in patients with idiopathic pulmonary fibrosis, because some preclinical studies have suggested that IFN-beta is a potent inhibitor of fibrogenesis, beneficial effects of IFN-beta have been expected. We therefore attempted to determine effects of IFN-beta and investigated the mechanism of action of IFN-beta in bleomycin-induced pulmonary fibrosis. Bleomycin at Day 0 and IFN-beta for 4 wk were administered intravenously to ICR mice. At 28 d after bleomycin injection, histologic and chemical analysis was performed for evaluation of effects of IFN-beta. Tissue distribution and amounts of TGF-beta1 and thrombospondin (TSP)-1/2 were analyzed. IFN-beta attenuated prolylhydroxylase activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced increase in TGF-beta1 in epithelial cells and extracellular matrix was attenuated by IFN-beta. TSP-1/2 was limited in platelets of control mice, but was present in foamy cells in fibrotic regions induced by bleomycin. These findings suggest that the antifibrotic effect of IFN-beta is inhibition of TGF-beta and its activation via decrease in TSP-1/2 in lung tissue and change in location of TSP-1/2 from platelets to foamy cells.