ABSTRACT
BACKGROUND AND OBJECTIVE: Various inflammatory mediators are involved in the development of cyclosporine A-induced gingival overgrowth. In this study, the gingival expression of cyclooxygenase-2 after cyclosporine A therapy was examined in vivo and in vitro. MATERIAL AND METHODS: After edentulous ridges on maxilla were established, 21 Sprague-Dawley rats received cyclosporine A daily for 4 wk, and a further 21 rats received solvent. After the rats were killed, the expression of cyclooxygenase-2 mRNA, interleukin-1beta mRNA, tumor necrosis factor-alpha mRNA, and interleukin-6 mRNA was examined in the edentulous gingiva. The expression of cyclooxygenase-2 protein and the production of prostaglandin E2 were also evaluated. RESULTS: In cultured human gingival fibroblasts and epithelial cells, the expression of cyclooxygenase-2 mRNA was measured after treatment with cyclosporine A. Significantly lower expression of cyclooxygenase-2 and interleukin-1beta mRNA, but higher interleukin-6 expression, were observed in gingiva from cyclosporine A-treated rats than in those from the control rats. Significantly less prostaglandin E2 production was observed in cyclosporine A-treated rats. Immunohistochemistry revealed that fewer gingival stromal cells were positively stained for cyclooxygenase-2 in cyclosporine A-treated rats. In cultured cells, significantly less cyclooxygenase-2 mRNA was detected after treatment with cyclosporine A. CONCLUSION: The expression of cyclooxygenase-2 was lower in the plaque nonretentive gingivae and the in vitro gingival cells upon treatment with cyclosporine A. Thus, we propose that cyclosporine A inhibits the expression of gingival cyclooxygenase-2.
Subject(s)
Cyclooxygenase 2 Inhibitors/pharmacology , Cyclosporine/pharmacology , Enzyme Inhibitors/pharmacology , Gingiva/enzymology , Adult , Animals , Blotting, Western , Cells, Cultured , Cyclooxygenase 2/analysis , Dinoprostone/analysis , Epithelial Cells/drug effects , Epithelial Cells/enzymology , Female , Fibroblasts/drug effects , Fibroblasts/enzymology , Gingiva/drug effects , Humans , Interleukin-1beta/analysis , Interleukin-6/analysis , Jaw, Edentulous/pathology , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Stromal Cells/drug effects , Stromal Cells/enzymology , Tumor Necrosis Factor-alpha/analysisABSTRACT
uinea pig antiserum specific to the purified bovine choline acetyltransferase was used to demonstrate the localization of this enzyme in rabbit forebrain by the peroxidase-antiperoxidase immunohistochemical method. Choline acetyltransferase was localized in olfactory bulb, olfactory tract, olfactory tubercle, piriform cortex, septum, diagonal band, basal ganglia, thalamus, hypothalamus, subthalamus, habenula, cerebral cortex, hippocampal region, corpus callosum, internal capsule, fornix, longitudinal striae and other areas. The findings reflect the distribution of cholinergic axons and, possibly, their terminals. These observations correlate well with biochemical determinations of choline acetyltransferase and with previously proposed cholinergic pathways.
