Thrombin-stimulated DNA Synthesis in Human Cultured Airway Smooth Muscle Occurs Independently of Products of Cyclo-oxygenase or 5-Lipoxygenase
Identifieur interne : 002479 ( Main/Exploration ); précédent : 002478; suivant : 002480Thrombin-stimulated DNA Synthesis in Human Cultured Airway Smooth Muscle Occurs Independently of Products of Cyclo-oxygenase or 5-Lipoxygenase
Auteurs : Darren Fernandes [Australie] ; Ross Vlahos [Australie] ; Alastair G. Stewart [Australie]Source :
- Pulmonary Pharmacology & Therapeutics [ 1094-5539 ] ; 2000.
English descriptors
- KwdEn :
- Teeft :
- Airway, Airway wall, Arachidonic, Arachidonic acid, Basal, Basal incorporation, Biol, Biol chem, Bwa4c, Cell cultures, Cell proliferation, Cpla2, Cysteinyl, Cysteinyl leukotrienes, Cytokine, Cytosolic phospholipase, Eicosanoid, Exogenous, Exogenous addition, Fernandes, Human airway, Incorporation, Inhibitor, Kinase, Leukotriene, Lipoxygenase, Lipoxygenase inhibition, Lipoxygenase inhibitors, Ltd4, Metabolism, Mitogen, Mitogenesis, Mitogenic, Muscle cells, Ndga, Pathway, Pge2, Pharmacol, Phospholipase, Physiol, Primaquine, Product formation, Proliferation, Prostaglandin, Receptor, Respir cell, Selective inhibitors, Smooth muscle mitogenesis, Thrombin, Thrombin response.
Abstract
Abstract: Arachidonic acid (AA) liberation and metabolism via cyclo-oxygenase or lipoxygenases may be an important regulatory pathway for mitogenic signalling in human cultured airway smooth muscle (ASM) cells. In cytokine-treated cells, thrombin markedly enhances production of the anti-mitogenic arachidonic acid metabolite, PGE2. In this study, in the absence of cytokines, we examined the role of endogenous AA metabolism in thrombin-stimulated ASM DNA synthesis. Selective inhibitors of cyclo-oxygenase of 5-lipoxygenase metabolism had no significant effect on 0.3 U/ml thrombin-stimulated DNA synthesis. However, the non-selective, redox-active lipoxygenase inhibitors NDGA and BWA4C inhibited thrombin-stimulated DNA synthesis. Under basal conditions, and following stimulation by thrombin, the levels of the AA metabolites PGE2, TxA2, and LTC4, remained below assay detection limits. Exogenous addition of AA, LTD4, or 5-, 12-, and 15-HETE and HpETE metabolites had no consistent or substantial stimulatory effect on either basal or thrombin-stimulated DNA synthesis. These data suggest that the non-selective lipoxygenase inhibitors influence DNA synthesis via effects unrelated to lipoxygenase inhibition. The lack of detection of AA metabolites, the lack of influence of selective antagonists/inhibitors of the AA pathway, and the failure of selected AA metabolites to either enhance or directly stimulate DNA synthesis suggest that in the absence of cytokines, cyclo-oxygenase and lipoxygenase metabolism has little role in signalling of human ASM DNA synthesis by thrombin.
Url:
DOI: 10.1006/pupt.2000.0251
Affiliations:
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In cytokine-treated cells, thrombin markedly enhances production of the anti-mitogenic arachidonic acid metabolite, PGE2. In this study, in the absence of cytokines, we examined the role of endogenous AA metabolism in thrombin-stimulated ASM DNA synthesis. Selective inhibitors of cyclo-oxygenase of 5-lipoxygenase metabolism had no significant effect on 0.3 U/ml thrombin-stimulated DNA synthesis. However, the non-selective, redox-active lipoxygenase inhibitors NDGA and BWA4C inhibited thrombin-stimulated DNA synthesis. Under basal conditions, and following stimulation by thrombin, the levels of the AA metabolites PGE2, TxA2, and LTC4, remained below assay detection limits. Exogenous addition of AA, LTD4, or 5-, 12-, and 15-HETE and HpETE metabolites had no consistent or substantial stimulatory effect on either basal or thrombin-stimulated DNA synthesis. These data suggest that the non-selective lipoxygenase inhibitors influence DNA synthesis via effects unrelated to lipoxygenase inhibition. The lack of detection of AA metabolites, the lack of influence of selective antagonists/inhibitors of the AA pathway, and the failure of selected AA metabolites to either enhance or directly stimulate DNA synthesis suggest that in the absence of cytokines, cyclo-oxygenase and lipoxygenase metabolism has little role in signalling of human ASM DNA synthesis by thrombin.</div></front></TEI><affiliations><list><country><li>Australie</li></country><region><li>Victoria (État)</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><region name="Victoria (État)"><name sortKey="Fernandes, Darren" sort="Fernandes, Darren" uniqKey="Fernandes D" first="Darren" last="Fernandes">Darren Fernandes</name></region><name sortKey="Stewart, Alastair G" sort="Stewart, Alastair G" uniqKey="Stewart A" first="Alastair G" last="Stewart">Alastair G. Stewart</name><name sortKey="Vlahos, Ross" sort="Vlahos, Ross" uniqKey="Vlahos R" first="Ross" last="Vlahos">Ross Vlahos</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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