?-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 ?-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 C? (PKC?). We then found that ?-CD inhibits binding of PKC? to diacylglycerol (DAG) via formation of a ?-CD-DAG complex, indicating that ?-CD inactivates PKC?. Furthermore, ?-CD controls activation of PKC? by reducing the recruitment of PKC? into the plasma membrane. Finally, ?-CD inhibits expression of intercellular and vascular cell adhesion molecule-1 by increasing NO via control of PKC?/eNOS and suppression of THP-1 cell adhesion to endothelial cells. These findings imply that ?-CD plays an important role in anti-inflammatory processes.

SUBMITTER: Jang S 

PROVIDER: S-EPMC7464935 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature