High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways
High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways
复制标题
DOI：
10.1038/aps.2010.174
复制
发表时间：
2011-02-01
影响因子：
8.2
通讯作者：
Wang, Xian
中科院分区：
文献类型：
--
作者：
Quan, Yi;Jiang, Chang-tao;Wang, Xian
目的：探讨高糖是否刺激炎症细胞因子的表达及其可能的机制。方法：采用ELISA和real-time PCR检测炎症因子的表达，化学发光法检测活性氧（ROS）的产生。结果：与低糖（10 mmol/L）相比，高糖（35 mmol/L）使原代培养的大鼠小胶质细胞中肿瘤坏死因子(TNF) α和单核细胞趋化蛋白-1 （MCP-1）的分泌增加，但白细胞介素(IL)-1 β和IL-6的分泌不增加，并呈时间依赖性。TNF α和MCP-1 mRNA的表达也在高糖反应中升高。这种上调是特定于高葡萄糖的，因为它在渗透控制中没有观察到。高糖处理刺激ROS的形成。此外，用活性氧清除剂NAC治疗可显著降低高糖诱导的TNF - α和MCP-1分泌。此外，核因子κ B （nf - κ B）抑制剂MG132和PDTC完全阻断高糖诱导的TNF α和MCP-1分泌。结论：高糖诱导体外大鼠小胶质细胞TNFa和MCP-1分泌及mRNA表达，其作用是通过ROS和nf - κ B通路介导的。
Aim: To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved.Methods: ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS).Results: Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)alpha and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1 beta and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNF alpha and MCP-1 also increased in response to high glucose. This upregulation was specific to high glucose because it was not observed in the osmotic control. High-glucose treatment stimulated the formation of ROS. Furthermore, treatment with the ROS scavenger NAC significantly reduced the high glucose-induced TNF alpha and MCP-1 secretion. In addition, the nuclear factor kappa B (NF-kappa B) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNF alpha and MCP-1 secretion.Conclusion: We found that high glucose induces TNFa and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-kappa B pathways.