ovalbumin and triptolide

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.

Topics: Airway Remodeling; Allergens; Animals; Asthma; Blotting, Western; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Diterpenes; Enzyme-Linked Immunosorbent Assay; Epoxy Compounds; Female; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Ovalbumin; Phenanthrenes; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

To explore the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in eosinophil inflammation of asthma airway.. Guinea pig models of asthma were established with aerosolized ovalbumin. A group of asthmatic guinea pigs were treated with injection of triptolide, density of eosinophil infiltration in airway tissues was observed under microscope and expression of GM-CSF mRNA in airway tissues was detected with dot hybridization by Dig-labeled cDNA probe.. Expression of GM-CSF mRNA in asthmatic animals were higher markedly than that in the triptolide-treated and the control groups. However, there was no statistically differences of density of eosinophils infiltration between the asthma and the triptolide-treated groups.. GM-CSF might participate in eosinophil inflammation in airway of asthmatic animals and triptolide might be of potential value in anti-inflammation for asthma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Diterpenes; Epoxy Compounds; Granulocyte-Macrophage Colony-Stimulating Factor; Guinea Pigs; Ovalbumin; Phenanthrenes; RNA, Messenger