| 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 |
Related Documents
:
|
14695024 - Difference in signal transduction mechanisms involved in 5-hydroxytryptamine- and u4661... 12746234 - Enhancement of alpha2-adrenoceptor-mediated vasoconstriction by the thromboxane-mimetic... 22439844 - Adenosine a2a receptor stimulation prevents hepatocyte lipotoxicity and nonalcoholic st... 2303424 - Phosphorylation by protein kinase c of the 20,000-dalton light chain of myosin in intac... 10995454 - Tor-mediated induction of autophagy via an apg1 protein kinase complex. 10233154 - Nuclear activities of basic fibroblast growth factor: potentiation of low-serum growth ... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-09-03 |
Journal Detail:
|
Title: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 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: 2011-06-15 |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Long-acting beta-agonists: a review of formoterol safety data from asthma clinical trials.
Next Document: Reference values for cardiopulmonary exercise testing in healthy volunteers: the SHIP study.