Pro-inflammatory Cytokines Induce Suppressor of Cytokine Signaling-3 in Human Periodontal Ligament Cells
Pro-inflammatory Cytokines Induce Suppressor of Cytokine Signaling-3 in Human Periodontal Ligament Cells
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DOI：
10.1016/j.joen.2010.02.027
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发表时间：
2010-06-01
影响因子：
4.2
通讯作者：
Anan, Hisashi
中科院分区：
文献类型：
--
作者：
Fukushima, Akie;Kajiya, Hiroshi;Anan, Hisashi
前言：根尖周炎是由牙髓损伤引起的，由牙周组织中的炎性细胞因子介导。另一方面，组织的破坏可以通过抑制促炎细胞因子的活性来防止。这些细胞因子和它们的反向调节分子之间的平衡被认为是调节组织破坏的因素。细胞因子信号转导抑制因子(SoCs)蛋白通过经典的负反馈环抑制炎性细胞因子信号转导。然而，在牙周病的发生发展过程中，它们是由炎性细胞因子诱导并调节的机制仍不清楚。我们研究了炎症细胞因子对人牙周膜(PDL)细胞SOCS蛋白表达的影响及其信号转导途径。方法：采用逆转录、实时定量聚合酶链式反应、Western印迹等方法检测炎性细胞因子对人PDL细胞SOCS表达及其信号转导途径的影响。此外，我们还用ELISA法检测了这些细胞因子诱导的SOCS-3是否抑制趋化因子的分泌。结果：炎性细胞因子IL-1β和IL-6诱导人PDL细胞SOCS-3的表达，但不诱导SOCS-2的表达。IL-1β和IL-6同时诱导PDL细胞分泌IL-8和单核细胞趋化蛋白-1，而SOCS-3过表达通过抑制下游信号通路的磷酸化而抑制这些趋化因子的分泌。结论：促炎细胞因子可诱导SOCS-3的表达。SOCS-3的诱导提示SOCS-3在负反馈中发挥重要作用，通过趋化因子依赖机制抑制根尖周炎牙周组织的严重破坏。(J截止2010年；36：1004-1008)
Introduction: Periapical inflammation is initiated by insult to the dental pulp and mediated by inflammatory cytokines in the periodontal tissue. On the other hand, the destruction of tissue can be prevented by the suppression of pro-inflammatory cytokine activity. The balance between these cytokines and their counterregulatory molecules has been suggested to regulate tissue destruction. Suppressors of cytokine signaling (SOCS) proteins are known to suppress inflammatory cytokine signaling via the classic negative feedback loop. However, the mechanism by which they are induced by inflammatory cytokines and regulated during the development of periodontal disease remains to be clarified. We investigated the effects of inflammatory cytokines on SOCS protein expression and their signaling pathways in human periodontal ligament (PDL) cells. Methods: We examined the effect of inflammatory cytokines on SOCSs expression and its signaling pathway in human PDL cells using reverse transcription- and real-time polymerase chain reaction, Western blot methods. Furthermore, we also examined whether these cytokines-induced SOCS-3 suppress chemokines secretion using ELISA methods. Results: We found that inflammatory cytokines interleukin (IL)-1 beta and IL-6 induced expression of SOCS-3 but not that of SOCS-2 in human PDL cells. IL-1 beta and IL-6 simultaneously induced IL-8 and monocyte chemoattractant protein-1 secretion in PDL cells, whereas SOCS-3 overexpression suppressed secretion of these chemokines through inhibition of phosphorylation in downstream signaling. Conclusion: The results suggest that pro-inflammatory cytokines induced SOCS-3 expression. The SOCS-3 induction suggests playing an important role in negative feedback, suppressing serious destruction of periodontal tissue in apical periodontitis through a chemokine-dependent mechanism. (J Ended 2010;36:1004-1008)