Back to Search
Start Over
Phenytoin potentiates interleukin-1-induced prostaglandin biosynthesis in human gingival fibroblasts.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 1992 Jul; Vol. 106 (3), pp. 574-8. - Publication Year :
- 1992
-
Abstract
- 1. The effect of phenytoin (PHT) on prostaglandin E2 (PGE2) biosynthesis in human gingival fibroblasts stimulated by interleukin-1 (IL-1 alpha, IL-1 beta) or by tumour necrosis factor alpha (TNF alpha) was studied. 2. IL-1 alpha (1.5-6.0 ng ml-1) and IL-1 beta (30-300 pg ml-1), dose-dependently, stimulated PGE2 formation, in 24 h cultures, with IL-beta being the most potent agonist. 3. PHT (2.5-20 micrograms ml-1) did not induce PGE2 formation itself but potentiated IL-1 alpha- and IL-1 beta-induced PGE2 formation in the gingival fibroblasts in a manner dependent on the concentrations of both IL-1 and PHT. 4. IL-1 beta (0.1-1.0 ng ml-1) induced release of [3H]-arachidonic acid ([3H]-AA) from prelabelled fibroblasts that was potentiated by PHT (20 micrograms ml-1). 5. TNF-alpha (greater than or equal to 0.01 micrograms ml-1) significantly stimulated the biosynthesis of PGE2 by a process that was potentiated by PHT. 6. Addition of exogenous arachidonic acid (AA) (greater than or equal to 1 microM) caused an increase of PGE2 formation in the fibroblasts that was not potentiated by PHT (20 micrograms ml-1). 7. The results indicate that treatment with PHT results in upregulation of prostaglandin biosynthesis in gingival fibroblasts challenged with IL-1 or TNF alpha, at least partly due to enhanced level of phospholipase A2 activity.
- Subjects :
- Arachidonic Acid metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Fibroblasts drug effects
Fibroblasts metabolism
Gingiva metabolism
Humans
Tritium
Tumor Necrosis Factor-alpha pharmacology
Dinoprostone biosynthesis
Gingiva drug effects
Interleukin-1 pharmacology
Phenytoin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 106
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 1504741
- Full Text :
- https://doi.org/10.1111/j.1476-5381.1992.tb14377.x