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FTY720 attenuates paraquat-induced lung injury in mice
Jie Qian1, Yan Ye2, Lixiong Lv1
1Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
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.
Insights
FTY720, an immune modulator, significantly reduced paraquat (PQ)-induced acute lung injury and fibrosis in mice. This treatment lowered key inflammatory markers and fibrotic indicators, suggesting therapeutic potential for PQ poisoning.
Area of Science:
- Toxicology
- Immunology
- Pulmonology
Background:
- Paraquat (PQ) poisoning is a severe condition primarily affecting the lungs, leading to irreversible fibrosis.
- Current treatments for PQ-induced lung injury are limited, necessitating the exploration of novel therapeutic agents.
- FTY720 is an immune modulator with potential anti-inflammatory and anti-fibrotic properties.
Purpose of the Study:
- To investigate the efficacy of FTY720 in mitigating paraquat-induced lung injury and fibrosis in a mouse model.
- To evaluate the impact of FTY720 on inflammatory and fibrotic markers in the lungs following paraquat exposure.
Main Methods:
- C57BL/6 mice were exposed to paraquat (PQ) and subsequently treated with FTY720.
- Groups included PQ alone, PQ + FTY720, FTY720 alone, and a control group.
- Lung tissues were analyzed histopathologically, biochemically, and immunohistochemically at day 3 and day 28 post-exposure.
Main Results:
- FTY720 treatment significantly attenuated PQ-induced acute lung injury and fibrosis, as evidenced by histopathology and Ashcroft scores.
- FTY720 reduced lung wet weight/body weight ratio, total protein, and inflammatory cytokines (IL-1β, IL-6, TNF-α) in bronchoalveolar lavage fluid on day 3.
- On day 28, FTY720 treatment downregulated key fibrotic markers including α-SMA, TGF-β, VEGF, Type-I Collagen, and Type-III Collagen.
Conclusions:
- FTY720 demonstrates significant therapeutic potential in reducing paraquat-induced lung injury and subsequent fibrosis in mice.
- The mechanism may involve the modulation of inflammatory responses and the suppression of fibrotic pathways.
- Further research is warranted to explore FTY720 as a clinical treatment for paraquat poisoning.
