Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein. Although TSPO expression is up-regulated during inflammation, the role of TSPO on vascular endothelial cell activation remains to be elucidated.Design and method:
In the present study, the phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation.Results:
Adenoviral TSPO overexpression inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-Tempo, a specific mitochondrial antioxidants, and cyclosporine A, a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam, TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells.Conclusions:
These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.