| IκB kinase β inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. | |
| | |
MedLine Citation:
|
PMID: 20573155 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
BACKGROUND: 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. OBJECTIVE: We examined the effects of a newly synthesized IKKβ inhibitor, IMD-0354, in a chronic allergen exposure model of bronchial asthma in mice. METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
| | |
Authors:
|
H Ogawa; M Azuma; S Muto; Y Nishioka; A Honjo; T Tezuka; H Uehara; K Izumi; A Itai; S Sone |
Related Documents
:
|
19047405 - Host cell cytokines induced by chlamydia pneumoniae decrease the expression of intersti... 12568495 - Non-allergic models of mucous cell metaplasia and mucus hypersecretion in rat nasal and... 16914605 - H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ... 20448835 - Antiproteases as therapeutics to target inflammation in cystic fibrosis. 619265 - Circulating immune complexes and complement activation in primary biliary cirrhosis. 19713215 - Regulation of immature dendritic cell migration by rhoa guanine nucleotide exchange fac... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology Volume: 41 ISSN: 1365-2222 ISO Abbreviation: Clin. Exp. Allergy Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8906443 Medline TA: Clin Exp Allergy Country: England |
Other Details:
|
Languages: eng Pagination: 104-15 Citation Subset: IM |
Copyright Information:
|
© 2010 Blackwell Publishing Ltd. |
Affiliation:
|
Department of Respiratory Medicine & Rheumatology Department of Molecular and Environmental Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan. ogawah@clin.med.tokushimau.ac.jp |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prognostic factors in adult acute lymphoblastic leukaemia.
Next Document: Anti-Asthma Simplified Herbal Medicine Intervention-induced long-lasting tolerance to allergen expos...