FTY720 attenuates paraquat-induced lung injury in mice

- FTY720 attenuated PQ-induced pathological damages in two phases.
- FTY720 curbed the production of inflammatory cytokines and total protein in BALF.
- FTY720 down-regulated biomarkers for pulmonary fibrosis.
- FTY720 showed no toxicity signs such as pathological lung lesions and weight loss.

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.