Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-9-12
pubmed:abstractText
Prostanoids are major regulators of smooth muscle function that are generated by cyclooxygenase (COX). Here we hypothesized that cytokines and mediators that regulate the pulmonary circulation would alter COX expression and prostanoid generation in pulmonary artery smooth muscle cells. Bradykinin, transforming growth factor-beta1 (TGF-beta1), and interleukin-1beta (IL-1beta) increased inducible COX-2 expression and prostaglandin E(2) (PGE(2)) release. Transfection studies using a COX-2 promoter construct demonstrated that all three agents acted transcriptionally. Constitutive COX-1 protein expression was unchanged. The COX inhibitor indomethacin, the COX-2 inhibitor NS-398, the protein synthesis inhibitor cycloheximide, and the glucocorticoid dexamethasone abrogated the increased PGE(2) levels. Dexamethasone and cycloheximide prevented COX-2 induction. Hypoxia (3% O(2)-5% CO(2)-92% N(2)) for 24 h selectively augmented TGF-beta1-stimulated PGE(2) production and COX-2 induction but had no effect alone. Prolonged hypoxic culture alone for 48 and 72 h enhanced COX-2 induction and increased PGE(2). These studies show that a number of stimuli are capable of inducing COX-2 in pulmonary artery smooth muscle cells. The interaction between hypoxia and TGF-beta1 may be particularly relevant to pulmonary hypertension.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L717-25
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12225948-Adult, pubmed-meshheading:12225948-Anoxia, pubmed-meshheading:12225948-Bradykinin, pubmed-meshheading:12225948-Cells, Cultured, pubmed-meshheading:12225948-Cyclooxygenase 2, pubmed-meshheading:12225948-Dinoprostone, pubmed-meshheading:12225948-Dose-Response Relationship, Drug, pubmed-meshheading:12225948-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12225948-Humans, pubmed-meshheading:12225948-Hypertension, Pulmonary, pubmed-meshheading:12225948-Interleukin-1, pubmed-meshheading:12225948-Isoenzymes, pubmed-meshheading:12225948-Male, pubmed-meshheading:12225948-Membrane Proteins, pubmed-meshheading:12225948-Muscle, Smooth, Vascular, pubmed-meshheading:12225948-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:12225948-Pulmonary Artery, pubmed-meshheading:12225948-Transcription, Genetic, pubmed-meshheading:12225948-Transforming Growth Factor beta, pubmed-meshheading:12225948-Transforming Growth Factor beta1
pubmed:year
2002
pubmed:articleTitle
Effect of bradykinin, TGF-beta1, IL-1beta, and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells.
pubmed:affiliation
Division of Respiratory Medicine, University of Nottingham, City Hospital, United Kingdom. dawn.bradbury@nottingham.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't