Cyclosporin A upregulates prostaglandin E2 production in human gingival fibroblasts challenged with tumor necrosis factor alpha in vitro.
The effect of cyclosporin A (CsA) on prostaglandin E2 (PGE2) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-alpha) was studied. TNF-alpha (1-100 ng/ml) dose-dependently stimulated PGE2 formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE2 formation itself but potentiated TNF-alpha induced PGE2 formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-alpha. TNF-alpha (10 ng/ml) stimulated the release of [3H]-arachidonic acid (AA) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 microM/ml) to the cells resulted in enhanced PGE2 formation that was not potentiated by CsA (100 ng/ml). Furthermore, CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-alpha (10 ng/ml), although PGE2 formation was enhanced. The results indicate that CsA and TNF-alpha act in concert on PGE2 formation in gingival fibroblasts, which may be of importance in the pathogenesis of gingival overgrowth induced by the drug.
Wondimu
B
B
Department of Pediatric Dentistry, Faculty of Odontology, Karolinska Institute, Huddinge, Sweden.
Modéer
T
T
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D016572:Cyclosporine / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019214:Gingival Overgrowth / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D016572:Cyclosporine; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone