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Mepacrine treatment attenuates allergic airway remodeling segregated from airway inflammation in mice.
MedLine Citation:
PMID:  21035433     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Asthma is a chronic airway disease characterized by increased airway hyperresponsiveness, airway inflammation, and airway remodeling including collagen deposition in subepithelial regions. We have shown earlier that mepacrine has anti-inflammatory activity and decreased the features of airway remodeling in a subacute model of asthma, when administered during the inflammatory phase. But it was not clear whether the reduction of airway remodeling by mepacrine was a direct effect or indirectly related to the reduction in the airway inflammation. In this study, we determined the effect of mepacrine on airway remodeling and airway hyperresponsiveness (AHR) in a chronic model of asthma which showed the features of airway inflammation in the initial stage (inflammation predominant stage) and airway remodeling with mild airway inflammation in a later stage (remodeling predominant stage). Mepacrine was administered only in the later stage that more accurately simulates human asthma, where airway remodeling already exists at the time of diagnosis. The remodeling predominant stage was associated with high levels of Th2 cytokines like IL-4 and IL-13, increase in the levels of profibrotic mediators such as arginase and TGF-β, and increased collagen deposition. These were efficiently attenuated by mepacrine treatment and led to a significant reduction in AHR. Thus, we conclude from this study that mepacrine has direct effects on established airway remodeling independent of its anti-inflammatory effects.
Authors:
Tanveer Ahmad; Ulaganathan Mabalirajan; Kanika Hasija; Balaram Ghosh; Anurag Agrawal
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Publication Detail:
Type:  Journal Article     Date:  2010-10-28
Journal Detail:
Title:  International immunopharmacology     Volume:  11     ISSN:  1878-1705     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  74-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
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