Effect of Endogenous and Exogenous Prostaglandin E2 on Interleukin-1 β –Induced Cyclooxygenase-2 Expression in Human Airway Smooth-Muscle Cells
| Autor: | Carola Buccellati, Giancarlo Folco, A. Hernandez, Francesca Fumagalli, Saula Ravasi, Serena Viappiani, Angelo Sala, Albino Bonazzi, Simona Zarini, G Chiesa, Manlio Bolla, Piero Zannini, T. Viganò |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Prostaglandins E
Synthetic Pulmonary and Respiratory Medicine medicine.medical_specialty Blotting Western Prostaglandin Bronchi Endogeny Cycloheximide Biology Critical Care and Intensive Care Medicine Dinoprostone chemistry.chemical_compound Internal medicine medicine Humans Prostaglandin E2 Cells Cultured Analysis of Variance Messenger RNA Membrane Proteins Interleukin Muscle Smooth Blotting Northern Molecular biology Isoenzymes Endocrinology Peroxidases chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Enzyme Induction biology.protein Arachidonic acid Cyclooxygenase Adenylyl Cyclases Interleukin-1 medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/ajrccm.162.6.2003127 |
| Popis: | We studied the effect of endogenous and exogenous prostaglandin E(2) (PGE(2)), a metabolite of arachidonic acid through the cyclooxygenase (COX) pathway, on interleukin (IL)-1 beta-induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE(2) resulted in enhanced expression of IL-1 beta-induced COX-2 protein and messenger RNA (mRNA) as compared with the effect of the cytokine per se. Inhibition of PGE(2) production with a nonselective COX inhibitor (flurbiprofen, 10 microM) resulted in a significant reduction in IL-1 beta- induced COX-2 expression, supporting a role of endogenous COX metabolites in the modulation of COX-2 expression. None of the experimental conditions used in the study affected the expression of constitutive cyclooxygenase (COX-1). Treatment with cycloheximide to inhibit translation, and with dexamethasone or actinomycin D to inhibit transcription, linked the effect of PGE(2) to the transcriptional level of COX-2 mRNA rather than to a potential effect on protein and/or mRNA stabilization. PGE(2) increased adenylate cyclase activity in a concentration dependent manner, and forskolin, a direct activator of adenylate cyclase, caused a marked increase in IL-1 beta-dependent COX-2, suggesting the existence of a causal relationship between the two events. The same results were observed with salbutamol, a bronchodilator that acts by increasing cyclic adenosine monophosphate. The effect of PGE(2) on COX-2 expression may contribute to the hypothesized antiinflammatory role of PGE(2) in human airways, providing a self-amplifying loop leading to increased biosynthesis of PGE(2) during an inflammatory event. |
| Databáze: | OpenAIRE |
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