High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-KB pathways  

作　　者：Yi QUAN Chang-tao JIANG Bing XUE Shi-gong ZHU Xian WANG 

机构地区：[1]Department of Physiology and Pathophysiology, School of Basic Medical Science [2]Key Laboratory of Molecular Cardiovascular Science, Ministry of Education [3]Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of the Ministry of Education, Peking University, Beijing 100191, China

出　　处：《Acta Pharmacologica Sinica》2011年第2期188-193,共6页中国药理学报（英文版）

摘　　要：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）α and monocyte chemotactic protein-1 （MCP-1）, but not interleukin （IL）-1β and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα 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 TNFα and MCP-1 secretion In addition, the nuclear factor kappa B （NF-KB） inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion. Conclusion： We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-KB pathways.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）α and monocyte chemotactic protein-1 （MCP-1）, but not interleukin （IL）-1β and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα 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 TNFα and MCP-1 secretion In addition, the nuclear factor kappa B （NF-KB） inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion. Conclusion： We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-KB pathways.

关 键 词：high glucose MICROGLIA tumor necrosis factor α monocyte chemotactic protein-2 reactive oxygen species NF-KB 

分 类 号：R[医药卫生]