Proinflammatory activation of macrophages by bisphenol A-glycidyl-methacrylate involved NFκB activation via PI3K/Akt pathway

Aim: 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.

► BisGMA is a potential agonist in RAW264.7 macrophage cells. ► BisGMA induced generation of proinflammatory cytokines, NO, and ROS. ► Up-regulation of iNOS expression. ► Up-regulation of NF-κB activation and IκB degradation. ► Up-regulation of Akt phosphorylation.