β-Cyclodextrin inhibits monocytic adhesion to endothelial cells through nitric oxide-mediated depletion of cell adhesion molecules

Abstract

Cyclodextrins (CDs) are used as drug delivery agents. In this study, we examined whether CDs have an inflammatory effect on endothelial cells. First, we found that β-CD promoted cell proliferation in bovine aortic endothelial cells and elevated nitric oxide (NO) production through dephosphorylation of threonine-495 (T-495) in endothelial nitric oxide synthetase (eNOS). Dephosphorylation of T-495 is known to activate eNOS. Phosphorylation of T-495 was found to be catalyzed by protein kinase Cϵ (PKCϵ). We then found that β-CD inhibits binding of PKCϵ to diacylglycerol (DAG) via formation of a β-CD-DAG complex, indicating that β-CD inactivates PKCϵ. Furthermore, β-CD controls activation of PKCϵ by reducing the recruitment of PKCϵ into the plasma membrane. Finally, β-CD inhibits expression of intercellular and vascular cell adhesion molecule-1 by increasing NO via control of PKCϵ/eNOS and suppression of THP-1 cell adhesion to endothelial cells. These findings imply that β-CD plays an important role in anti-inflammatory processes.