Interferon-β Inhibits Bleomycin-Induced Lung Fibrosis by Decreasing Transforming Growth Factor-β and Thrombospondin
| Autor: | Yasushi Miyauchi, Kohei Ueda, Arata Azuma, Shu Hashimoto, Ying-Ji Li, Shinji Abe, Saburo Sone, Shoji Kudoh, Satoshi Henmi, Jiro Usuki, Akiko Izawa, Kuniko Matsuda |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Pulmonary Fibrosis Clinical Biochemistry Procollagen-Proline Dioxygenase Lung injury Bleomycin Thrombospondin 1 Transforming Growth Factor beta1 Mice chemistry.chemical_compound Idiopathic pulmonary fibrosis Transforming Growth Factor beta Interferon Pulmonary fibrosis medicine Animals Lung Molecular Biology Mice Inbred ICR Thrombospondin Antibiotics Antineoplastic business.industry Epithelial Cells Interferon-beta Cell Biology medicine.disease Immunohistochemistry Extracellular Matrix Mechanism of action chemistry Immunology Cancer research medicine.symptom Thrombospondins business Foam Cells medicine.drug Transforming growth factor |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 32:93-98 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2003-0374oc |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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