P120 catenin attenuates lipopolysaccharide-induced blood-brain barrier dysfunction and inflammatory responses in human brain microvascular endothelial cells.

Increasing evidences suggest that p120 catenin (p120ctn) exerts important functions in the regulation of pro-inflammatory molecules. However, the relationship among p120ctn, inflammatory responses and blood-brain barrier (BBB) dysfunction as they are the initiator of sepsis is not unknown. In this study, we found that p120ctn expression was correlated with an increase in the permeability of BBB and a decrease in the expression of tight-junction proteins in human brain microvascular endothelial cells (HBMECs) after LPS challenge. Transfection with p120ctn small interfering RNA (siRNA) induced disruption of BBB integrity, monocyte migration across BBB and inflammatory responses at basal level and after LPS treatment. Conversely, over-expression of p120ctn with adenovirus significantly ameliorated BBB disruption and inflammatory responses in LPS-treated cells. Mechanistically, up-regulation of p120ctn inhibited LPS-induced NF-κB activation by suppressing IKKβ and IκBα phosphorylation, IκBα degradation. Therefore, we conclude that p120ctn improves the BBB dysfunction and inflammatory responses through the inhibition of NF-κB activation, suggesting that forced p120ctn expression may provide a novel therapeutic strategy to attenuate LPS-induced BBB compromise and sepsis.