Interleukin-17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6/TBK1-JNK/NF-κB pathways
Interleukin-17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6/TBK1-JNK/NF-κB pathways
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DOI：
10.1111/imm.12395
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发表时间：
2015-03-01
期刊：
影响因子：
6.4
通讯作者：
Xu, Yan
中科院分区：
文献类型：
--
作者：
Lin, Danping;Li, Lu;Xu, Yan
白细胞介素-17 （IL-17或IL-17A）是一种由T辅助型17细胞产生的多效细胞因子，参与多种自身免疫性和炎症性疾病的发病机制，包括牙周炎。虽然在牙周炎中的促炎能力已被广泛研究，但IL-17的其他生物学功能，包括其在骨重塑中的作用及其潜在的分子机制，尚未得到很好的阐明。在本研究中，IL-17可显著增强人牙周韧带细胞中核因子- κ B配体受体激活因子（RANKL）的表达和抑制破骨细胞发生的两个关键指标osteoprotegerin （OPG）的表达，提示IL-17可能在牙周骨重塑的发病机制中发挥破坏性作用。靶向丝裂原活化蛋白激酶、Akt或核因子κ B信号的药物信号抑制剂可抑制il -17诱导的RANKL和OPG调控。值得注意的是，RANKL的增强被c-Jun n -末端激酶和核因子κ B信号抑制剂显著阻断。用小干扰RNA进一步研究上游信号。肿瘤坏死因子受体相关因子6和TNF受体相关因子（TRAF）家族成员相关核因子kappa-轻链增强子活化B细胞（NF-kappa B）激活因子（TANK）结合激酶1被发现是人牙周韧带细胞中il -17依赖性RANKL调控的关键信号分子。这些发现有助于全面了解IL-17在牙周炎发病机制中的作用，也可能为牙周炎的治疗提供合理的途径。
Interleukin-17 (IL-17 or IL-17A), a pleiotropic cytokine produced by T helper type 17 cells, is involved in the pathogenesis of various autoimmune and inflammatory disorders, including periodontitis. Although the ability of pro-inflammation in periodontitis has been widely investigated, the other biological functions of IL-17, including its role in bone remodelling and the underlying molecular mechanisms, have not been well clarified. In the present study, IL-17 could significantly enhance the expression of receptor activator for nuclear factor-kappa B ligand (RANKL) and inhibit the expression of osteoprotegerin (OPG) in human periodontal ligament cells, the two critical indicators for osteoclastogenesis, suggesting that IL-17 may play a destructive role in the pathogenesis of periodontal bone remodelling. Pharmaceutical signal inhibitors targeted at mitogen-activated protein kinases, Akt or nuclear factor-kappa B signals, inhibited IL-17-induced RANKL and OPG regulation. Notably, the enhancement of RANKL was significantly blocked by the inhibitors of c-Jun N-terminal kinase and nuclear factor-kappa B signals. The upstream signals were further investigated with the small interfering RNA. Both tumour necrosis factor receptor-associated factor 6 and TNF receptor associated factor (TRAF) family member-associated nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappa B) activator (TANK)-binding kinase 1 were found to be the critical signal molecules for IL-17-dependent RANKL regulation in human periodontal ligament cells. These findings may provide comprehensive understanding of the role of IL-17 in the pathogenesis of periodontitis and might also provide a reasonable route for periodontitis therapy.