Author(s)

Keisuke Miyamoto, Sadatomo Tasaka, Yasushi Nakano, Hiromi Shinoda, Hirofumi Kamata, Wakako Yamasawa, Makoto Ishii, Naoki Hasegawa, Tomoko Betsuyaku

Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan.
Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan.
Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan.

Background and Objectives: Peroxisome proliferator-activated receptor-g (PPAR-g) is a nuclear receptor whose activation regulates inflammation and fibrosis in various organs. We aimed to investigate the effect of two PPAR-g ligands, telmisartan and rosiglitazone, on lung injury and fibrosis induced by intratracheal bleomycin (BLM). Methods: Lung injury and fibrosis was induced in female C57Bl/6 mice by intratracheal instillation of 1.0 mg/kg of BLM. Some of the animals received rosiglitazone intraperitoneally or telmisartan in drinking water. Bronchoalveolar lavage (BAL) was performed 2, 7, 14 or 21 days after BLM instillation for cell counting and measurement of mediators in the lung. In a separate series, the lungs were sampled for collagen assay and histopathological evaluation. Results: Treatment with rosiglitazone or telmisartan significantly attenuated the BLM-induced increases in lung collagen content, pathological score, and inflammatory cells in BAL fluid. Rosiglitazone significantly suppressed BLM-induced elevation of TGF-b₁, MCP-1, and IL-6 levels in the lung. In contrast, telmisartan made no changes in these cytokines, whereas it mitigated the BLM-induced increase in prostaglandin F_2a in the lung. Higher concentrations of rosiglitazone and telmisartan attenuated proliferation of lung fibroblasts in vitro. Conclusions: Two PPAR-g ligands, rosiglitazone and telmisartan, exert protective effects on BLM-induced lung fibrosis through the suppression of different profibrotic mediators.

Peroxisome Proliferator-Activated Receptor-γ; Bleomycin; Pulmonary Fibrosis; Transforming Growth Factor-β₁; Prostaglandin F_2α

Miyamoto, K. , Tasaka, S. , Nakano, Y. , Shinoda, H. , Kamata, H. , Yamasawa, W. , Ishii, M. , Hasegawa, N. and Betsuyaku, T. (2013) Differential Mechanisms of the Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Bleomycin-Induced Lung Fibrosis. Open Journal of Respiratory Diseases, 3, 31-38. doi: 10.4236/ojrd.2013.32006.