Fig. 3

Schematic illustrating the role of cav-1 in different cell. In endothelial cells, after exposure to LPS, cav-1 interacts with toll-like receptor 4 (TLR4), and then TLR4 promotes activation of MyD88, leading to NF-κB activation and the generation of proinflammatory cytokines. Under normal condition, cav-1 inhibits eNOS. If eNOS is activated, NO will nitrate IRAK4 which is a signaling factor required for NF-κB activation. And cav-1 in microglia can induce the internalization of SVCT2 which is the primary mediator of vitamin C uptake in neurons, triggering a proinflammatory phenotype in microglia and inducing microglia activation. Whereas in macrophages, cav-1decreases proinflammatory cytokine production and augments anti-inflammatory production through the TLR4/MKK3/p38 MAPK pathway. Besides, TLR4 activation by LPS also stimulates HO-1 transporting to the caveolae and producing CO which has anti-inflammatory effects and augments the cav-1/TLR4 interaction in murine macrophages. Toll-like receptor 4 (TLR4), interleukin-1 receptor associated kinase 4 (IRAK4), heme oxygenase-1 (HO-1), carbon oxide (CO), plasma membrane sodium-vitamin C cotransporter 2 (SVCT2)