Sukkar T Z, Thomason J M, Cawston T E, Lakey R, Jones D, Catterall J, Seymour R A
School of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.
J Periodontal Res. 2007 Dec;42(6):580-8. doi: 10.1111/j.1600-0765.2007.00986.x.
Cyclosporin-induced gingival overgrowth arises from an alteration in collagen homeostasis and is enhanced by inflammatory changes in the gingival tissues. The aim of this study was to investigate the interaction among interleukin-1, oncostatin M, cyclosporin and nifedipine in promoting the up-regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase by gingival fibroblasts.
Fibroblast cultures (n = 5) were obtained from healthy controls and from patients with cyclosporin-induced gingival overgrowth, and cells were harvested between the fourth and ninth passages. Cells were stimulated with interleukin-1 and oncostatin M, alone or in combination, and with different concentrations of cyclosporin (0-2000 ng/mL) and nifedipine (0-200 ng/mL). MMP-1 and tissue inhibitor of metalloproteinase-1 production was determined using an enzyme-linked immunosorbent assay technique. A CyQuant cell proliferation assay was used to determine the DNA concentration in the sample.
Fibroblasts obtained from patients with cyclosporin-induced gingival overgrowth produced significantly lower levels of MMP-1 than control fibroblasts (p < 0.001); tissue inhibitor of metalloproteinase-1 levels were significantly lower (p < 0.05), and the ratio of MMP-1 to tissue inhibitor of metalloproteinase-1 was reduced, in the conditioned medium of patients with cyclosporin-induced gingival overgrowth compared with controls. Interleukin-1 and oncostatin M produced a significant increase in the up-regulation of MMP-1, which was reversed when cyclosporin and nifedipine were added to the cell cultures (p < 0.05).
Pro-inflammatory cytokines significantly up-regulate MMP-1 in cultured gingival fibroblasts. Up-regulation is attenuated by both cyclosporin and nifedipine. The interaction may account for the synergism between inflammation and cyclosporin-induced gingival overgrowth.
环孢素诱导的牙龈过度生长源于胶原稳态的改变，并因牙龈组织的炎症变化而加剧。本研究的目的是探讨白细胞介素-1、抑瘤素M、环孢素和硝苯地平在促进牙龈成纤维细胞上调基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂方面的相互作用。
从健康对照者和环孢素诱导的牙龈过度生长患者中获取成纤维细胞培养物（n = 5），并在第4至第9代之间收获细胞。用白细胞介素-1和抑瘤素M单独或联合刺激细胞，并用不同浓度的环孢素（0 - 2000 ng/mL）和硝苯地平（0 - 200 ng/mL）刺激。使用酶联免疫吸附测定技术测定MMP-1和金属蛋白酶组织抑制剂-1的产生。使用CyQuant细胞增殖测定法测定样品中的DNA浓度。
从环孢素诱导的牙龈过度生长患者中获得的成纤维细胞产生的MMP-1水平明显低于对照成纤维细胞（p < 0.001）；与对照组相比，环孢素诱导的牙龈过度生长患者的条件培养基中金属蛋白酶组织抑制剂-1水平明显降低（p < 0.05），且MMP-1与金属蛋白酶组织抑制剂-1的比值降低。白细胞介素-1和抑瘤素M使MMP-1的上调显著增加，当将环孢素和硝苯地平添加到细胞培养物中时，这种上调被逆转（p < 0.05）。
促炎细胞因子显著上调培养的牙龈成纤维细胞中的MMP-1。环孢素和硝苯地平均减弱这种上调。这种相互作用可能解释了炎症与环孢素诱导的牙龈过度生长之间的协同作用。
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