TY - JOUR T1 - Disruption of Nrf2 enhances susceptibility to pulmonary fibrosis induced by bleomycin in mice JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p783 AU - Ying-Ji Li AU - Takako Shimizu AU - Yukiyo Hirata AU - Hirofumi Inagaki AU - Arata Azuma AU - Hajime Takizawa AU - Satoru Takahashi AU - Masayuki Yamamoto AU - Tomoyuki Kawada AU - Shoji Kudoh Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p783.abstract N2 - Introduction: Recently studies suggest that N-acetylcysteine improve the idiopathic pulmonary fibrosis. Oxidant/antioxidant balances may play an important role in many of the processes of inflammation and fibrosis. Nrf2 is involved in the transcriptional regulation of many antioxidant genes. We therefore investigated the role of Nrf2 against the development of pulmonary fibrosis in mice.Materials and methods: Both Nrf2–/– and Nrf2+/+ C57BL/6J mice were used. Bleomycin was administered intravenously to the mice at a dosage of 0, 70, 80, and 90 mg/kg body weight on day 0, and the fibroblastic foci were assessed histologically by Ashcroft score determined in the lung tissues on day 28. Furthermore, bleomycin was administered intravenously to the mice at a dosage of 80 mg/kg body weight on day 0, and the bronchoalveolar lavage (BAL) fluid examined for cell populations on days 0, 3, 7, 10, 14, 21, and 28.Results: The fibroblastic foci were induced by bleomycin at a dosage of 90mg/kg body weight in the lung tissues on day 28 in Nrf2+/+ mice. In contrast, the fibroblastic foci were induced by bleomycin at a dosage of 70mg/kg body weight in Nrf2–/– mice. The total number of cells and macrophages in the BAL fluid were significantly increased from day7 after bleomycin administered in both Nrf2+/+ and Nrf2–/– mice. The increased cells number were significantly greater in Nrf2+/+ mice than in Nrf2–/– mice.Conclusions: These findings suggest that Nrf2 might be an important genetic factor in the determination of susceptibility to bleomycin induced pulmonary fibrosis by regulating the macrophages defense mechanisms. ER -