NO regulates LPS-stimulated cyclooxygenase gene expression and activity in pulmonary artery endothelium
| Autor: | Brian W. Christman, Leonard C. Berry, Barbara Meyrick, Paul R. Myers, Jian-Xiong Chen, Miles A. Tanner |
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| Rok vydání: | 2001 |
| Předmět: |
Lipopolysaccharides
Pulmonary and Respiratory Medicine Time Factors Endothelium Physiology Gene Expression Prostaglandin Pulmonary Artery Biology Pharmacology Nitric Oxide Nitric oxide chemistry.chemical_compound Physiology (medical) medicine.artery medicine Animals Nitric Oxide Donors Cyclic GMP Cells Cultured Cell Biology Isoenzymes Endothelial stem cell medicine.anatomical_structure Eicosanoid chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Immunology Pulmonary artery Cyclooxygenase 1 Prostaglandins biology.protein Cattle Endothelium Vascular Cyclooxygenase Blood vessel |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 280:L450-L457 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.2001.280.3.l450 |
| Popis: | We examined whether nitric oxide (NO) inhibits prostanoid synthesis through actions on cyclooxygenase (COX) gene expression and activity. Bovine pulmonary artery endothelial cells were pretreated for 30 min with the NO donors 1 mM S-nitroso- N-acetylpenicillamine (SNAP), 0.5 mM sodium nitroprusside (SNP), or 0.2 μM spermine NONOate; controls included cells pretreated with either 1 mM N-acetyl-d-penicillamine or the NO synthase (NOS) inhibitor 1 mM N G-nitro-l-arginine methyl ester with and without addition of lipopolysaccharide (LPS; 0.1 μg/ml) for 8 h. COX-1 and COX-2 gene and protein expression were examined by RT-PCR and Western analysis, respectively; prostanoid measurements were made by gas chromatography-mass spectrometry, and COX activity was studied after a 30-min incubation with 30 μM arachidonic acid. LPS induced COX-2 gene and protein expression and caused an increase in COX activity and an eightfold increase in 6-keto-PGF1αrelease. LPS-stimulated COX-2 gene expression was decreased by ∼50% by the NO donors. In contrast, LPS caused a significant reduction in COX-1 gene expression and treatment with NO donors had little effect. SNAP, SNP, and NONOate significantly suppressed LPS-stimulated COX activity and 6-keto-PGF1α release. Our data indicate that increased generation of NO attenuates LPS-stimulated COX-2 gene expression and activity, whereas inhibition of endogenous NOS has little effect. |
| Databáze: | OpenAIRE |
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