title: Proinflammatory activation of macrophages by bisphenol A-glycidyl-methacrylate involved NFκB activation via PI3K/Akt pathway.
abstract: OBJECTIVE
  Bisphenol A-glycidyl-methacrylate (BisGMA), a dental composite resin and dentin bonding agent, might prompt inflammatory effects to adjacent tissues. Macrophages are a major cellular component of the inflammatory sites. Little is known about the mechanisms of BisGMA on macrophages activation. The aim of this study was to evaluate BisGMA on proinflammatory mediators generation of murine macrophage RAW264.7 cells.
  
  
  METHODS
  IL-1β and IL-6 were analyzed by enzyme-linked immunosorbent assay. Nitric oxide, extracellular superoxide anion, and intracellular reaction oxygen species were measured by Griess assay, ferricytochrome c, and 2',7'-dichlorofluorescein assay, respectively. Expression of iNOS, p-p65, IκB, and p-Akt was analyzed by Western blotting.
  
  
  RESULTS
  BisGMA augmented the generation of IL-1β, IL-6, nitric oxide and the expression of iNOS in a time- and dose-dependent manner (p<0.05). BisGMA enhanced the generation of intracellular and extracellular ROS in a dose-dependent manner (p<0.05). The levels of p65 phosphorylation, IκB degradation, and Akt phosphorylation were found to be increased in a time- and dose-dependent manner (p<0.05).
  
  
  CONCLUSIONS
  These results indicate that BisGMA could induce nitric oxide, ROS, and inflammatory cytokines in macrophages. In addition, BisGMA may active macrophage via NF-κB activation, IκB degradation, and p-Akt activation.
authors.affiliation: Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Kuan
authors.forename: Fu-Mei
authors.initials: FM
authors.lastname: Huang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Li
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000818:Animals; D017438:Bisphenol A-Glycidyl Methacrylate / Q000009:adverse effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D017438:Bisphenol A-Glycidyl Methacrylate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt