title: High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways.
abstract: OBJECTIVE
  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-κB) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion.
  
  
  CONCLUSIONS
  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-κB pathways.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Beijing, China. yquan226@gmail.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Quan
authors.forename: Chang-tao
authors.initials: CT
authors.lastname: Jiang
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.forename: Shi-gong
authors.initials: SG
authors.lastname: Zhu
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008163:Luminescent Measurements; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose