RRC ID 41351
Author Fujimori Y, Maeda S, Saeki M, Morisaki I, Kamisaki Y.
Title Inhibition by nifedipine of adherence- and activated macrophage-induced death of human gingival fibroblasts.
Journal Eur J Pharmacol
Abstract The effects of nifedipine on the death and proliferation of gingival fibroblasts were investigated to elucidate the mechanism of gingival overgrowth that is associated with chronic administration of Ca2+ channel blockers. The number of adhered viable and dead fibroblasts obtained from healthy human gingiva increased after confluence, whereas cell death was inhibited by nifedipine in a concentration-dependent manner. A similar inhibition was also observed in the presence of other calcium channel blockers, such as nicardipine, diltiazem, and verapamil. When gingival fibroblasts were co-cultured with RAW264 (macrophage-like) cells, lipopolysaccharide (LPS) caused the concentration-dependent death of fibroblasts. Nifedipine significantly inhibited the LPS-induced cell death. Although neither LPS nor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitroso-hydrazino)-ethanamine, a nitric oxide donor, directly caused fibroblast death, 3-morpholino-sydnonimine (SIN-1), a peroxynitrite donor, induced fibroblast death, regardless of the presence of RAW cells. The cell death induced by SIN-1 was not affected by nifedipine treatment. LPS stimulation caused an increase in the immunoreactivity of inducible nitric oxide synthase (iNOS) and in the nitrite concentration in the incubation medium of RAW cells. The induction of iNOS was completely prevented by the incubation with nifedipine. The inhibition by nifedipine of nitrite production in RAW cells was also observed after treatment with nicardipine, but not with either diltiazem or verapamil. Therefore, the inhibition by nifedipine of both adherence- and LPS-stimulated macrophage-induced death of fibroblasts may be the mechanism of gingival overgrowth seen during chronic treatment with Ca(2+) channel blockers.
Volume 415(1)
Pages 95-103
Published 2001-3-9
DOI 10.1016/s0014-2999(01)00810-x
PII S0014-2999(01)00810-X
PMID 11245857
MeSH Animals Calcium Channel Blockers / pharmacology* Cell Adhesion / drug effects* Cell Death / drug effects* Cell Division / drug effects Cell Line Cells, Cultured Coculture Techniques DNA Fragmentation / drug effects Diltiazem / pharmacology Dose-Response Relationship, Drug Fibroblasts / cytology Fibroblasts / drug effects* Fibroblasts / metabolism Gingiva / cytology Gingiva / drug effects Humans Lipopolysaccharides / pharmacology Macrophages / cytology Macrophages / physiology* Nicardipine / pharmacology Nifedipine / pharmacology* Nitric Oxide / metabolism Nitric Oxide Donors / pharmacology Thymidine / metabolism Time Factors Verapamil / pharmacology
IF 3.263
Times Cited 21
Human and Animal Cells RAW 264(RCB0535)