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IκB kinase β inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma.
- Source :
- Clinical & Experimental Allergy; Jan2011, Vol. 41 Issue 1, p104-115, 12p, 1 Color Photograph, 2 Charts, 5 Graphs
- Publication Year :
- 2011
-
Abstract
- Nuclear factor (NF)-κB is a transcription factor that regulates cytokine and chemokine production in various inflammatory diseases, including bronchial asthma. IκB kinase (IKK) β is important for NF-κB activation in inflammatory conditions, and is possibly related to airway remodelling. Thus, inhibition of the IKKβ-NF-κB pathway may be an ideal strategy for the management of airway remodelling. We examined the effects of a newly synthesized IKKβ inhibitor, IMD-0354, in a chronic allergen exposure model of bronchial asthma in mice. A chronic mouse model was generated by challenge with house dust mite antigen ( Dermatophagoides pteronyssinus). IMD-0354 was administrated intraperitoneally in therapeutic groups. Lung histopathology, hyperresponsiveness and the concentrations of mediators and molecules in supernatants of lung homogenates were determined. NF-κB activation was inhibited by prolonged periods of IMD-0354 administration. IMD-0354 reduced the numbers of bronchial eosinophils. IMD-0354 also inhibited the pathological features of airway remodelling, including goblet cell hyperplasia, subepithelial fibrosis, collagen deposition and smooth muscle hypertrophy. Inhibition of these structural changes by IMD-0354 was the result of the suppressing the production and activation of remodelling-related mediators, such as TGF-β, via inhibition of IKKβ. IMD-0354 inhibited IL-13 and IL-1β production, and it restored the production of IFN-γ. It also ameliorated airway hyperresponsiveness. IKKβ plays crucial roles in airway inflammation and remodelling in a chronic mouse model of asthma. A specific IKKβ inhibitor, IMD-0354, may be therapeutically beneficial for treating airway inflammation and remodelling in chronic asthma. Cite this as: H. Ogawa, M. Azuma, S. Muto, Y. Nishioka, A. Honjo, T. Tezuka, H. Uehara, K. Izumi, A. Itai and S. Sone, Clinical & Experimental Allergy, 2011 (41) 104-115. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09547894
- Volume :
- 41
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Allergy
- Publication Type :
- Academic Journal
- Accession number :
- 55811360
- Full Text :
- https://doi.org/10.1111/j.1365-2222.2010.03564.x