| Cholinergic receptor and cyclic stretch-mediated inflammatory gene expression in intact ASM. | |
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MedLine Citation:
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PMID: 16339998 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We tested the hypothesis that cholinergic stimulation and cyclic stretch regulate inflammatory gene expression in intact airway smooth muscle by measuring mRNA expression in bovine tracheal smooth muscle using limited microarray analysis and RT-PCR. Carbachol (1 microM) induced significant increases in the expression of cyclooxygenase (COX)-1, COX-2, IL-8, and plasminogen activator, urokinase type (PLAU) to levels ranging from 1.3- to 3.1-fold of control. Sinusoidal length oscillation at an amplitude of 10% muscle length and a frequency of 1 Hz induced significant increases in the expression of CCL-2, COX-2, IL-1 beta, and IL-6 to levels ranging from 12- to 206-fold of control. Decreasing the oscillatory amplitude by 50% did not significantly change inflammatory gene expression. In contrast, decreasing the oscillatory frequency by 50% significantly attenuated inflammatory gene expression by 76-93%. Nifedipine (1 microM) had an insignificant effect on carbachol-induced gene expression, but significantly inhibited sinusoidal length oscillation-induced inflammatory gene expression by 40-78%. Correlation analysis revealed two groups of genes with differential responses to sinusoidal length oscillation. The highly responsive group included COX-2, IL-6, and IL-8, which exhibited 45- to 364-fold increases in gene expression in response to sinusoidal length oscillation. The moderately responsive group included CCL2 and PLAU, which exhibited 13- to 19-fold increases in gene expression in response to sinusoidal oscillation. These findings suggest that cyclic stretch regulates inflammatory gene expression in intact airway smooth muscle in an amplitude- and frequency-dependent manner by modulating the activity of L-type voltage-gated calcium channels. |
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Authors:
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Jeannette Kanefsky; Marc Lenburg; Chi-Ming Hai |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2005-12-09 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 34 ISSN: 1044-1549 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-03-20 Completed Date: 2006-06-13 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 417-25 Citation Subset: IM |
Affiliation:
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Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Box G-B3, Providence, RI 02912, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium Channel Blockers / pharmacology Calcium Channels, L-Type / drug effects, physiology Carbachol / pharmacology Cattle Chemokine CCL2 / biosynthesis, genetics Cholinergic Agonists / pharmacology Cyclooxygenase 1 / biosynthesis, genetics Cyclooxygenase 2 / biosynthesis, genetics Gene Expression Regulation Interleukins / biosynthesis, genetics Muscle Contraction Muscle, Smooth / metabolism, physiology* Nifedipine / pharmacology Oligonucleotide Array Sequence Analysis RNA, Messenger / biosynthesis Receptors, Cholinergic / biosynthesis*, genetics Stress, Mechanical Trachea / metabolism, physiology* Urokinase-Type Plasminogen Activator / biosynthesis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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HL-52714/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Chemokine CCL2; 0/Cholinergic Agonists; 0/Interleukins; 0/RNA, Messenger; 0/Receptors, Cholinergic; 21829-25-4/Nifedipine; 51-83-2/Carbachol; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 3.4.21.73/Urokinase-Type Plasminogen Activator |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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