Synergistic activation of lipopolysaccharide-stimulated glial cells by propofol

•Propofol synergistically increased NO and ROS production in LPS-stimulated glial cells.•Propofol also increased the expression of iNOS, MMP-9, IL-6 and IL-1β.•The effects were mediated by JNK and p38 activation.•The activated microglial cells may induce neuronal cell death. Despite the extensive use of propofol in general anesthetic procedures, the effects of propofol on glial cell were not completely understood. In lipopolysaccharide (LPS)-stimulated rat primary astrocytes and BV2 microglial cell lines, co-treatment of propofol synergistically induced inflammatory activation as evidenced by the increased production of NO, ROS and expression of iNOS, MMP-9 and several cytokines. Propofol augmented the activation of JNK and p38 MAPKs induced by LPS and the synergistic activation of glial cells by propofol was prevented by pretreatment of JNK and p38 inhibitors. When we treated BV2 cell culture supernatants treated with LPS plus propofol on cultured rat primary neuron, it induced a significant neuronal cell death. The results suggest that the repeated use of propofol in immunologically challenged situation may induce glial activation in brain.