Molecular mechanisms involved in the regulation of prostaglandin biosynthesis by glucocorticoids.
The anti-inflammatory properties of glucocorticoids are attributed in part, to their interference with prostaglandin synthesis. Phospholipases A2 and cyclooxygenases, the key enzymes of prostaglandin biosynthesis, are targets of glucocorticoid action; the molecular mechanisms, however, are not yet understood in detail. Obviously, glucocorticoids can act at different levels of gene regulation depending on cell type and inducing stimulus. The current knowledge of glucocorticoid interference with phospholipase A2 and cyclooxygenase expression is summarized. In comparison with other nonsteroidal anti-inflammatory drugs, glucocorticoids are unique inasmuch as they also inhibit cytokine synthesis and expression of other inflammation-related enzymes. Based on a more detailed understanding of glucocorticoid action, it may be possible to therapeutically exploit the anti-inflammatory effects and at the same time avoid the unwanted metabolic actions of these steroids.
Goppelt-Struebe
M
M
Universität Erlangen-Nürnberg, Erlangen, Germany.
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005938:Glucocorticoids; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2