title: Cyclosporin A and phenytoin modulate inflammatory responses.
abstract: Gingival overgrowth is a common side-effect of administration of the immunosuppressant cyclosporin A and the anti-epileptic drug phenytoin. While cyclosporin-induced gingival overgrowth is often accompanied by gingival inflammation, phenytoin-induced gingival overgrowth usually forms fibrotic lesions. To determine whether these drugs alter the inflammatory responses of gingival fibroblasts, we investigated the effects of cyclosporin and phenytoin on Toll-like receptor (TLR)-mediated responses to microbial components. In Chinese hamster ovary reporter cell lines, cyclosporin alone triggered signaling, whereas phenytoin down-regulated signaling induced by the TLR2 or TLR4 ligand. In human gingival fibroblasts, cyclosporin alone did not induce evident inflammatory responses, but augmented the expression of CD54 and the production of interleukin (IL)-6 and IL-8 induced by TLR ligands, whereas phenytoin attenuated those responses. Cyclosporin also augmented CD54 expression in gingiva of mice injected with lipopolysaccharide. These results indicated that cyclosporin positively and phenytoin negatively modulated inflammatory responses of human gingival fibroblasts.
authors.affiliation: Department of Periodontology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: A M M
authors.initials: AM
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation; D004926:Escherichia coli; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D005881:Gingiva / Q000187:drug effects* / Q000276:immunology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis / Q000187:drug effects; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010672:Phenytoin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects; D051193:Toll-Like Receptors / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D016209:Interleukin-8; D008050:Lipid A; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018799:Intercellular Adhesion Molecule-1; D010672:Phenytoin; D016572:Cyclosporine