Interleukin-12 Induces Receptor Activator of Nuclear Factor-Kappa B Ligand Expression by Human Periodontal Ligament Cells
Interleukin-12 Induces Receptor Activator of Nuclear Factor-Kappa B Ligand Expression by Human Periodontal Ligament Cells
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DOI：
10.1902/jop.2017.160813
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发表时间：
2017-07-01
影响因子：
4.3
通讯作者：
Pavasant, Prasit
中科院分区：
文献类型：
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作者：
Ayuthaya, Benjar Issaranggun Na;Everts, Vincent;Pavasant, Prasit
背景：促炎细胞因子白介素 (IL)-12 水平升高与牙周炎的严重程度相关。然而，IL-12 在牙周病中的可能作用尚未明确。本研究的目的是研究 IL-12 是否影响人牙周膜 (hPDL) 细胞中核因子 kappa B (NF-kappa B) 配体 (RANKL) 受体激活剂 (RANKL) 的表达，这是一种有效的破骨细胞刺激因子。方法：为了确定 IL-12 的作用，将 hPDL 细胞与重组人 IL-12 (p70) 以剂量（0 至 10 ng/mL）和时间依赖性孵育方式。在 mRNA 和蛋白质水平评估 RANKL 的表达。通过使用特定的抑制剂来确定IL-12的潜在信号通路。结果：在IL-12的影响下，hPDL细胞表达显着更高水平的RANKL。表达由信号转导子和转录激活子 4 和 NF-kB 信号通路介导。 IL-12 孵育细胞的条件培养基被证明含有诱导 RANKL 表达的分子。添加苏拉明（G 蛋白偶联受体抑制剂）和乙二醇四乙酸（钙螯合剂）表明存在中间分子，可以激活钙依赖性途径中的异三聚体 G 蛋白信号传导。结论：IL-12 处理后 hPDL 细胞的 RANKL 表达显着增加。因此，这项研究支持免疫系统和骨骼系统之间密切的相互关系，并表明 IL-12 在牙周病发病机制中的溶骨作用。
Background: Increased level of proinflammatory cytokine interleukin (IL)-12 correlates with the severity of periodontitis. Yet, a possible role of IL-12 in periodontal disease has not been clarified. The aim of this study is to investigate whether IL-12 affects expression of receptor activator of nuclear factor-kappa B (NF-kappa B) ligand (RANKL), a potent osteoclaststimulating factor, by human periodontal ligament (hPDL) cells.Methods: To determine the effect of IL-12, hPDL cells were incubated with recombinant human IL-12 (p70) in a dose-(0 to 10 ng/mL) and time-dependent manner. Expression of RANKL was evaluated at mRNA and protein levels. Underlying signaling pathways of IL-12 were determined by using specific inhibitors.Results: Under the influence of IL-12, hPDL cells expressed significantly higher levels of RANKL. Expression was mediated by signal transducer and activator of transcription 4 and NF-kB signaling pathways. Conditioned medium of IL-12-incubated cells proved to contain molecule(s) that induced RANKL expression. Addition of suramin (G protein-coupled receptor inhibitor) and ethylene glycol tetraacetic acid (calcium chelator) suggested existence of intermediate molecule(s) that could activate heterotrimeric G protein signaling in a calcium-dependent pathway.Conclusions: Expression of RANKL by hPDL cells significantly increased after IL-12 treatment. Therefore, this study supports a close interrelationship between immune and skeletal systems and suggests an osteolytic role of IL-12 in pathogenesis of periodontal disease.