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: Jie Qian, Yan Ye, Lixiong Lv, Changqing Zhu, Shuang Ye
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 21 Issue 2 Pg. 426-31 (Aug 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24893116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Actins
• Collagen Type I
• Collagen Type III
• Interleukin-1beta
• Interleukin-6
• Propylene Glycols
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• alpha-smooth muscle actin, mouse
• Fingolimod Hydrochloride
• Sphingosine
• Paraquat

Topics

• Actins (metabolism)
• Acute Lung Injury
• Animals
• Body Weight (drug effects)
• Bronchoalveolar Lavage Fluid (chemistry)
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Disease Models, Animal
• Fingolimod Hydrochloride
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Lung (drug effects, metabolism)
• Lung Injury (chemically induced, drug therapy, metabolism)
• Mice
• Mice, Inbred C57BL
• Paraquat (adverse effects)
• Propylene Glycols (pharmacology)
• Pulmonary Edema (chemically induced, drug therapy, metabolism)
• Pulmonary Fibrosis (drug therapy, metabolism)
• Sphingosine (analogs & derivatives, pharmacology)
• Transforming Growth Factor beta (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Vascular Endothelial Growth Factor A