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Phenytoin potentiates interleukin‐1‐induced prostaglandin biosynthesis in human gingival fibroblasts
Author(s) -
Modéer Thomas,
Brunius Gustaf,
Iinuma Mitsuo,
Lerner Ulf H.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14377.x
Subject(s) - phenytoin , interleukin 1β , biosynthesis , prostaglandin , pharmacology , chemistry , endocrinology , medicine , interleukin , biochemistry , biology , cytokine , neuroscience , enzyme , epilepsy
1 The effect of phenytoin (PHT) on prostaglandin E 2 (PGE 2 ) biosynthesis in human gingival fibroblasts stimulated by interleukin‐1 (IL‐1α, IL‐1β) or by tumour necrosis factor α (TNFα) was studied. 2 IL‐1α (1.5–6.0 ng ml −1 ) and IL‐1β (30–300 pg ml −1 ), dose‐dependently, stimulated PGE 2 formation, in 24 h cultures, with IL‐β being the most potent agonist. 3 PHT (2.5–20 μg ml −1 ) did not induce PGE 2 formation itself but potentiated IL‐1α‐ and IL‐1β‐induced PGE 2 formation in the gingival fibroblasts in a manner dependent on the concentrations of both IL‐1 and PHT. 4 IL‐1β (0.1–1.0 ng ml −1 ) induced release of [ 3 H]‐arachidonic acid ([ 3 H]‐AA) from prelabelled fibroblasts that was potentiated by PHT (20 μg ml −1 ). 5 TNF‐α (≥0.01 μg ml −1 ) significantly stimulated the biosynthesis of PGE 2 by a process that was potentiated by PHT. 6 Addition of exogenous arachidonic acid (AA) (≥ 1 μ m ) caused an increase of PGE 2 formation in the fibroblasts that was not potentiated by PHT (20 μg ml −1 ). 7 The results indicate that treatment with PHT results in upregulation of prostaglandin biosynthesis in gingival fibroblasts challenged with IL‐1 or TNFα, at least partly due to enhanced level of phospholipase A 2 activity.