title: Effects of montelukast on subepithelial/peribronchial fibrosis in a murine model of ovalbumin induced chronic asthma.
abstract: Montelukast, a leukotriene receptor antagonist, is used commercially as a maintenance treatment for asthma and to relieve allergic symptoms. In this study, we evaluated the protective effects of montelukast against the airway inflammation and fibrosis using a murine model of ovalbumin (OVA) induced chronic asthma. The animals received OVA challenge three times a week for 4 weeks. Montelukast (30 mg/kg) was administrated orally once a day for 4 weeks. The administration of montelukast caused a reduction in elevated interleukin (IL)-4, IL-13, eotaxin, immunoglobulin (Ig), inflammatory cell infiltration into the airways, and mucus production after repeated OVA challenges. To investigate the antifibrotic mechanism of montelukast, we examined the expression of profibrotic mediators, including vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and Smad3 proteins in the lung tissue using western blotting and immunohistochemistry. The administration of montelukast reduced the overexpression of profibrotic proteins in the lung tissue, which was confirmed by immnunohistochemistry. These results are consistent with a histopathological examination of lung tissue with Masson's trichrome stain. In conclusion, the administration of montelukast reduced airway inflammation and pulmonary fibrosis by reducing the release of Th2 cytokines and the expression of VEGF, TGF-β1/Smad3 in the lung tissue.
authors.affiliation: Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, 483 Expo-ro, Yusung-gu, Daejeon 305-811, Republic of Korea.
authors.forename: In Sik
authors.initials: IS
authors.lastname: Shin
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Jeon
authors.forename: Hyeun Kyoo
authors.initials: HK
authors.lastname: Shin
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D000485:Allergens / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003521:Cyclopropanes; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000276:immunology; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D051900:Smad3 Protein / Q000276:immunology; D013440:Sulfides; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D000085:Acetates; D000485:Allergens; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D016207:Cytokines; D020024:Leukotriene Antagonists; D011804:Quinolines; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D013440:Sulfides; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin; C093875:montelukast
keywords: Chronic asthma; Pulmonary fibrosis; Samd3; Transforming growth factor; Vascular endothelial growth factor