title: Enhancement of LPS-induced microglial inflammation response via TLR4 under high glucose conditions.
abstract: BACKGROUND
  Microglia activation mediated by toll-like receptor 4 (TLR4) plays an important role in neuroinflammation and postoperative cognitive dysfunction (POCD). Diabetes mellitus (DM) has been recently suggested as an independent risk factor for POCD. In this study, we investigate the potential exacerbation of the inflammatory response in primary microglia due to high glucose conditions.
  
  
  METHODS
  Primary microglial cells were exposed to normal glucose (25 mmol/L) and high glucose (35 mmol/L) levels alone or with lipopolyscaccharide (LPS 0, 2, 5, 10 ng/mL). The pro-inflammatory response of the cells was assessed by measuring changes in cytokine levels and the evaluation of associated signaling pathways.
  
  
  RESULTS
  Neither high glucose nor low LPS (≤5 ng/ml) alone had an effect on TNF-a and IL-6 levels, but the combination of low LPS and high glucose stimulated the inflammatory response. Analyses of the associated signaling pathways demonstrated that high glucose enhanced the LPS-induced microglial activation via the TLR4/JAK2/STAT3 pathway.
  
  
  CONCLUSIONS
  This study demonstrates that high glucose, one of the key abnormalities characteristic of DM, can augment LPS-induced microglial activation and inflammatory cytokine levels through the TLR4/JAK2/STAT3 pathway, offering new insight into the pathophysiological relationship between DM and POCD.
authors: Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Xiang
authors: X
authors: Zhang
authors: Hongquan
authors: H
authors: Dong
authors: Susu
authors: S
authors: Zhang
authors: Shunmei
authors: S
authors: Lu
authors: Jie
authors: J
authors: Sun
authors: Yanning
authors: Y
authors: Qian
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D053614:Janus Kinase 2; D005947:Glucose