Likewise, an in vitro rat BBB model constituted with BMECs and astrocytes has revealed that the infection of astrocytes with JEV causes the release of not only IL-6 and vascular endothelial growth factor, which transduce signals to activate the ubiquitin-proteasome pathway for intracellular degradation of the cytoplasmic TJ protein ZO-1 in BMECs, but also MMP2 and MMP9, which are critical for extracellular degradation of the transmembrane TJ protein claudin-5 on the surface of BMECs [349]. The gene discussed is IL6; the disease is infection.