Mechanism of astrocytes and lymphocytes in the blood-brain barrier of multiple sclerosis

Objective To investigating the interactions between astrocytes(AS)and lymphocytes(LCs) at the blood-brain barrier(BBB) on the pathogenesis of multiple sclerosis (MS). Methods Primary rat brain microvascular endothelial cells (rBMECs) and AS isolated from SD rats were used to establish BBB models in vitro.Trans-endothelial electrical resistance (TEER) and permeability were compared between an rBMEC mono-culture and rBMEC/AS co-culture, to evaluate the validity of each as a BBB cell model.rBMEC/LCs co-culture and rBMEC/AS/LCs tri-culture were established to evaluate the inflammatory response in MS by measuring the expression of nerve growth factor (NGF), matrix metalloproteinase (MMP)-2, MMP-9, interleukin (IL)-17, interferon γ (IFN-γ), and forkhead box P3 (Foxp3). Results The rBMEC/AS co-culture was exhibited a higher TEER value(>300 Ωcm2) and lower lymphocyte permeability(<200 000) than did the rBMEC mono-culture.Compared to the rBMEC mono-culture, the rBMEC/AS/LCs tri-culture showed significantly decreased the expression of NGF, IL-17, and IFN-γ and increased the expression of MMP-2 and Foxp3(P=0.036; P=0.022). Conclusion The results suggest that the interaction between AS and LCs may increase the expression of MMP-2 and decrease expression of IL-17 and IFN-γ at the BBB.Furthermore, the rBMEC/AS/LCs tri-culture promted the synergistic effect between AS and LCS may be involved in the pathogenesis of MS. Key words: Blood-brain barrier; Endothelial cells; Trans-endothelial electrical