Mycophenolate mofetil and triptolide alleviating airway inflammation in asthmatic model mice partly by inhibiting bone marrow eosinophilopoiesis

Mao, Hui; Chen, Xue rong; Yi, Qun; Li, Su yun; Wang, Zeng Li; Li, Fuyu

doi:10.1016/j.intimp.2008.03.009

Cited by 14 publications

(8 citation statements)

References 33 publications

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“…Triptolide treatment has also been shown to be effective in lung inflammation and injury models. Triptolide reduced pulmonary eosinophilic inflammation in mice sensitized and challenged with ovalbumin (12). A water-soluble form of triptolide inhibited inflammatory cell infiltrates and obliterative bronchiolitis in a tracheal allograft model (9).…”

Section: Discussionmentioning

confidence: 99%

Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation

Hoyle

Chen

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Inflammation is associated with various pulmonary diseases and contributes to the pathogenesis of acute lung injury. We previously identified a proinflammatory signaling pathway triggered by G protein-coupled receptors (GPCRs) in which stimulation of G(q)-coupled GPCRs results in activation of the transcription factor NF-kappaB. Because damage to the lung causes the release of multiple mediators acting through G(q)-coupled GPCRs, this signaling pathway is likely to contribute to inflammatory processes in the injured lung. In an effort to identify novel inhibitors of lung inflammation, the National Institutes of Health Clinical Collection, a library of 446 compounds, was screened for inhibitory activity toward production of IL-8 induced by stimulation of the G(q)-coupled tachykinin 1 receptor with substance P in A549 cells. Twenty-eight compounds that significantly inhibited substance P-induced IL-8 production were identified. The most potent inhibitor was triptolide, a diterpenoid compound from Tripterygium wilfordii Hook F, a vine used in traditional Chinese medicine for the treatment of autoimmune diseases. Triptolide inhibited IL-8 production induced by substance P with an IC(50) of 2.3 x 10(-8) M and inhibited NF-kappaB activation in response to an agonist of the protease-activated receptor 2 with an IC(50) of 1.4 x 10(-8) M. Anti-inflammatory effects of triptolide were assessed in vivo using a chlorine gas lung injury model in mice. Triptolide inhibited neutrophilic inflammation and the production of KC (Cxcl1) in the lungs of chlorine-exposed mice. The results demonstrate that triptolide exhibits anti-inflammatory activity in cultured lung cells and in an in vivo model of acute lung injury.

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Section: Discussionmentioning

confidence: 99%

Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation

Hoyle

Chen

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Triptolide has the effects of inhibiting proliferation and inducing apoptosis 9–11 . Clinical and basic studies have been performed to investigate the usefulness of triptolide in the treatment of asthma 12–14 . We previously showed that triptolide inhibited pulmonary inflammation in patients with steroid‐resistant asthma and some studies indicate that triptolide can relieve pulmonary pathology and control the progress of asthma airway remodelling 15 .…”

Section: Introductionmentioning

confidence: 99%

The effects of triptolide on airway remodelling and transforming growth factor-β1/Smad signalling pathway in ovalbumin-sensitized mice

Chen

Jiang

2011

Immunology

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Summary 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‐β1 were assessed by immunohistology and ELISA, levels of TGF‐β1 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‐β1, TGF‐β1 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.

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“…GATA3 is selectively expressed in Th2 cells and is a vital transcription factor during Th2 cell differentiation. The expression of GATA3 promotes precursor T‐cell differentiation into Th2 cells in the absence of STAT6 . GATA3 can simultaneously promote IL‐4, IL‐5 and IL‐13 gene expression in Th2 cells, and the inhibition of GATA3 significantly downregulates cytokine expression .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of interleukin‐13 gene expression by triptolide in activated T lymphocytes

et al. 2013

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Mycophenolate mofetil and triptolide alleviating airway inflammation in asthmatic model mice partly by inhibiting bone marrow eosinophilopoiesis

Cited by 14 publications

References 33 publications

Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation

Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation

The effects of triptolide on airway remodelling and transforming growth factor-β1/Smad signalling pathway in ovalbumin-sensitized mice

Inhibition of interleukin‐13 gene expression by triptolide in activated T lymphocytes

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