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      PGE 2 Synthesis by Corneal Endothelial Cells: Effect of Glucocorticoids and NSAIDs

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          The aim of this work was to study the effect of various anti-inflammatory drugs on PGE<sub>2</sub> synthesis in cultured bovine corneal endothelial cells (BCECs) stimulated with calcium ionophore A<sub>23187</sub> or lipopolysaccharide (LPS) of Salmonella typhimurium. NSAIDs were more potent in inhibiting LPS-stimulated PGE<sub>2</sub> synthesis. Diclofenac was more potent than indomethacin, although both drugs showed a 98% maximal inhibitory effect. Dexamethasone inhibited 80% of the A<sub>23187</sub>-stimulated PGE<sub>2</sub> synthesis and only 53% of the LPS-stimulated PGE<sub>2</sub> synthesis. Prednisolone did not show an inhibitory effect. The results demonstrate the inhibitory effect of NSAIDs and show differences between the activity of glucocorticoids on PGE<sub>2</sub> synthesis in BCECs. Prednisolone could not inhibit PGE<sub>2</sub> synthesis in these cells in our experimental conditions.

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          Cyclooxygenase-2: regulation and relevance in inflammation.

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            Anti-inflammatory actions of steroids: molecular mechanisms

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              Proinflammatory cytokines regulate cyclooxygenase-2 mRNA expression in human macrophages.

              Prostaglandins play a major role in the inflammatory and immune response. Macrophages constitutively produce prostaglandins by the enzyme cyclooxygenase-1 (cox) whereas inflammatory mediators and cytokines stimulate the inducible enzyme cox-2 for high output prostaglandin production. In this study, we investigated the effect of LPS, IFN-gamma and TNF-alpha in the regulation of cox-1 and cox-2 mRNA expression in PMA-differentiated U937 human macrophages. LPS, but not IFN-gamma or TNF-alpha, caused the induction of cox-2 mRNA in a dose- and time-dependent fashion. In IFN-gamma-primed macrophages, LPS stimulated a marked increase in the accumulation of cox-2 mRNA, whereas TNF-alpha and IFN-gamma induced a moderate level. However, IFN-gamma in combination with either LPS or TNF-alpha induced a synergistic increase in the accumulation of cox-2 mRNA after 24 hours. Regardless of the conditions, cox-1 mRNA remained unchanged. These results indicate that IFN-gamma priming is required for full expression of cox-2 mRNA in response to LPS or TNF-alpha stimulation and suggest that cox-2 mRNA is highly regulated by cytokines during macrophage activation.

                Author and article information

                Ophthalmic Res
                Ophthalmic Research
                S. Karger AG
                February 1999
                02 December 1998
                : 31
                : 1
                : 42-46
                Departamento I de Optica, Universidad de Alicante, España
                55511 Ophthalmic Res 1999;31:42–46
                © 1998 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 2, References: 16, Pages: 5
                Original Paper


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