HMGB1 increases myelin debris phagocytosis and ICAM-1 expression in rat CNS endothelial cells in vitro via the TLR4/NF-κB pathway

Abstract

Abstract HMGB1 regulates the inflammatory response after CNS injury. We aimed to determine the effect and mechanism of HMGB1 on the phagocytosis of myelin debris and the expression of ICAM-1 mediated by myelin debris in endothelial cells.The expression of MBP, CatD, and ICAM-1, as well as macrophage adhesion to endothelial cells, were studied in myelin debris-mediated endothelial cells and the role of TLR4/NF-κB signaling pathway in the regulation of these proteins expression by HMGB1 in myelin debris-mediated endothelial cells .The expression of MBP, CatD, and ICAM-1 in myelin debris-mediated endothelial cells was significantly increased following rHMGB1 exposure. The expression of MBP, CatD, ICAM-1, and macrophagocyte adhesion in myelin debris-mediated endothelial cells without rHMGB1 exposure was significantly reduced. The expression of MBP, CatD, and ICAM-1, and macrophagocyte adhesion were increased in endothelial cells first incubated with rHMGB1 for 24h and then treated with myelin debris. HMGB1 effects on these proteins expression in myelin debris-mediated endothelial cells in vitro were mediated, at least in part, by activation of the TLR4/NF-κB signaling pathway.HMGB1 increased MBP, CatD and ICAM-1 expression, as well as myelin debris phagocytosis and macrophage adhesion in myelin debris-mediated endothelial cells in vitro. These effects occur through the HMGB1/TLR4/NF-κB signaling pathway.