title: The effects of triptolide on airway remodelling and transforming growth factor-β₁/Smad signalling pathway in ovalbumin-sensitized mice.
abstract: Airway remodelling contributes to increased morbidity and mortality in asthma. We have reported that triptolide, the major component responsible for the immunosuppressive and anti-inflammatory effects of Tripterygium wilfordii Hook F, inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether triptolide inhibits airway remodelling in a mouse asthma model and observed the effects of triptolide on the transforming growth factor-β₁ (TGF-β₁)/Smad pathway in ovalbumin (OVA)-sensitized mice. BALB/c mice were sensitized to intraperitoneal OVA followed by repetitive OVA challenge for 8 weeks. Treatments included triptolide (40 μg/kg) and dexamethasone (2 mg/kg). The area of bronchial airway (WAt/basement membrane perimeter) and smooth muscle (WAm/basement membrane perimeter), mucus index and collagen area were assessed 24 hr after the final OVA challenge. Levels of TGF-β(1) were assessed by immunohistology and ELISA, levels of TGF-β(1) mRNA were measured by RT-PCR, and levels of pSmad2/3 and Smad7 were assessed by Western blot. Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway and smooth muscle, mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β(1) , TGF-β(1) mRNA and pSmad2/3 were significantly reduced in mice treated with triptolide and dexamethasone, and this was associated with a significant increase in levels of Smad7. Triptolide may function as an inhibitor of asthma airway remodelling. It may be a potential drug for the treatment of patients with a severe asthma airway.
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Lv
authors.forename: Shanping
authors.initials: S
authors.lastname: Jiang
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects* / Q000276:immunology; D000485:Allergens / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D010616:Phenanthrenes / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D051785:Smad Proteins / Q000096:biosynthesis* / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D000485:Allergens; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C001899:triptolide; D003907:Dexamethasone; D010047:Ovalbumin