title: FTY720 attenuates paraquat-induced lung injury in mice.
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 (0.1mg/kg, ip) solution 2h after PQ exposure and twice a week for 4 consecutive weeks; 3) FTY720 group (n=5): FTY720 (0.1mg/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.
authors.affiliation: Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China; Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Lixiong
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. Electronic address: zhuchangqing_renji@126.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China. Electronic address: yeshuang_renij@126.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ye
mesh_terms: D000199:Actins / Q000378:metabolism; D055371:Acute Lung Injury; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010269:Paraquat / Q000009:adverse effects*; D011409:Propylene Glycols / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D053583:Interleukin-1beta; D015850:Interleukin-6; D011409:Propylene Glycols; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D010269:Paraquat
keywords: FTY720; Lung injury; Paraquat poisoning