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

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.