Document Detail


Steroids augment relengthening of contracted airway smooth muscle: potential additional mechanism of benefit in asthma.
MedLine Citation:
PMID:  18768574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Breathing (especially deep breathing) antagonises development and persistence of airflow obstruction during bronchoconstrictor stimulation. Force fluctuations imposed on contracted airway smooth muscle (ASM) in vitro result in its relengthening, a phenomenon called force fluctuation-induced relengthening (FFIR). Because breathing imposes similar force fluctuations on contracted ASM within intact lungs, FFIR represents a likely mechanism by which breathing antagonises bronchoconstriction. While this bronchoprotective effect appears to be impaired in asthma, corticosteroid treatment can restore the ability of deep breaths to reverse artificially induced bronchoconstriction in asthmatic subjects. It has previously been demonstrated that FFIR is physiologically regulated through the p38 mitogen-activated protein kinase (MAPK) signalling pathway. While the beneficial effects of corticosteroids have been attributed to suppression of airway inflammation, the current authors hypothesised that alternatively they might exert their action directly on ASM by augmenting FFIR as a result of inhibiting p38 MAPK signalling. This possibility was tested in the present study by measuring relengthening in contracted canine tracheal smooth muscle (TSM) strips. The results indicate that dexamethasone treatment significantly augmented FFIR of contracted canine TSM. Canine tracheal ASM cells treated with dexamethasone demonstrated increased MAPK phosphatase-1 expression and decreased p38 MAPK activity, as reflected in reduced phosphorylation of the p38 MAPK downstream target, heat shock protein 27. These results suggest that corticosteroids may exert part of their therapeutic effect through direct action on airway smooth muscle, by decreasing p38 mitogen-activated protein kinase activity and thus increasing force fluctuation-induced relengthening.
Authors:
O J Lakser; M L Dowell; F L Hoyte; B Chen; T L Lavoie; C Ferreira; L H Pinto; N O Dulin; P Kogut; J Churchill; R W Mitchell; J Solway
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-03
Journal Detail:
Title:  The European respiratory journal     Volume:  32     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-03     Completed Date:  2009-05-08     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1224-30     Citation Subset:  IM    
Affiliation:
Dept of Paediatrics, University of Chicago, MC4064, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. olakser@peds.bsd.uchicago.edu
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MeSH Terms
Descriptor/Qualifier:
Airway Obstruction / drug therapy,  pathology
Animals
Asthma / metabolism*
Bronchoconstriction
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Dogs
Lung / pathology
Muscle, Smooth / metabolism*
Phosphorylation
Signal Transduction
Steroids / metabolism*
Stress, Mechanical
Trachea / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism
Grant Support
ID/Acronym/Agency:
AI 56352/AI/NIAID NIH HHS; HD 043387/HD/NICHD NIH HHS; HL 79368/HL/NHLBI NIH HHS; K12 HD043387-03/HD/NICHD NIH HHS; P01 AI056352-05/AI/NIAID NIH HHS; R01 HL079398-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Steroids; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases
Comments/Corrections
Comment In:
Eur Respir J. 2008 Nov;32(5):1135-7   [PMID:  18978129 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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