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Objective Myelin debris mediates the expression of intercellular adhesion molecule-1 (ICAM-1) in endothelial cells of the central nervous system (CNS) after disease and injury and plays a critical role in promoting the recruitment of peripheral immune cells. As an inflammatory necrosis factor, high mobility group box-1 (HMGB1) regulates the inflammatory response after CNS injury. Therefore, 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. Methods Rat brain and spinal cord microvascular endothelial cells were cultured in vitro. The expression of myelin basic protein (MBP), cathepsin D (CatD), and ICAM-1, as well as macrophage adhesion to endothelial cells, were studied in myelin debris-mediated endothelial cells with or without recombinant HMGB1 (rHMGB1) exposure, at different times. The role of the toll-like receptor 4 (TLR4) / nuclear factor-kappa B (NF-κB) signaling pathway in the regulation of MBP, CatD, and ICAM-1 expression by HMGB1 in myelin debris-mediated endothelial cells was also studied. Results The expression of MBP, CatD, and ICAM-1 in myelin debris-mediated endothelial cells was significantly increased from 12 to 72 h following rHMGB1 exposure, with a peak increase observed at the 24 h time point. The expression of MBP, CatD, ICAM-1, and macrophagocyte adhesion in myelin debris-mediated endothelial cells without rHMGB1 exposure was significantly reduced compared with those in the 24 h rHMGB1 + myelin debris group. Moreover, the expression of MBP, CatD, and ICAM-1, and macrophagocyte adhesion were significantly increased in endothelial cells first incubated with rHMGB1 for 24 h and then treated with myelin debris than in the myelin debris group. The HMGB1 effects on MBP, CatD, and ICAM-1 expression in myelin debris-mediated endothelial cells in vitro were mediated, at least in part, by activation of the TLR4/NF-κB signaling pathway. Conclusion 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. |
