FTY720 attenuates paraquat-induced lung injury in mice |
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| Institution: | 1. Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China;2. Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China;1. College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, P. R. China;2. Postdoctoral Research Station of Clinical Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, P. R. China;3. Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, P. R. China;4. School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, P. R. China;5. Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing, P. R. China;1. Department of Pharmacology, School of Basic Medicine Sciences, Tianjin Medical University, Tianjin 300070, China;2. Logistics University of Chinese People''s Armed Police Forces, Tianjin 300309, China;3. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin 300162, China;4. Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Tianjin 300192, China;5. Peking Union Medical College, Tianjin 300192, China;1. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Logistic University of Chinese People''s Armed Police Force, Tianjin 300162, China;2. Logistics University of Chinese People''s Armed Police Force, Tianjin 300162, China;3. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin, 300162, China;4. Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, Tianjin First Center Hospital, Tianjin 300192, China |
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| Abstract: | Paraquat (PQ) poisoning, with the lung as a primary target organ, is a devastating disease which irreversibly progresses to diffuse alveolitis followed by extensive lung fibrosis. In the present study, we aimed to investigate the effect of FTY720, an immune modulator, on PQ-induced lung injury in mice. C57BL/6 mice were randomized into four groups: 1) PQ group (n = 12): mice was instilled with PQ (30 mg/kg, ip); 2) PQ + FTY720 group (n = 12): animals received FTY720 (0.1 mg/kg, ip) solution 2 h after PQ exposure and twice a week for 4 consecutive weeks; 3) FTY720 group (n = 5): FTY720 (0.1 mg/kg, ip) was administrated twice a week for 4 consecutive weeks; and 4) Control group (n = 10): same volumes of saline were injected. Mice were sacrificed on either day 3 or day 28 for histopathological, biochemical and immunohistochemical analyses of lung damage indicators. We found that FTY720 treatment attenuated PQ-induced acute lung injury and lung fibrosis as evaluated by histopathological changes and Ashcroft score. On day 3, FTY720 administration reduced PQ-induced increases in lung wet weight/body weight (LW/BW), total protein and cytokine levels including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalceolar lavage fluid (BALF). On day 28, the expressions of alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) detected by immunohistochemistry, as well as the mRNA levels of α-SMA, Type-I Collagen and Type-III Collagen examined by Real-time PCR were down-regulated after FTY720 treatment. These results indicate that FTY720 could attenuate PQ-induced lung injury, but further investigation is necessary. |
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