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.

Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients

“…Nitric oxide is, besides many other essential functions in different concentration ranges, a powerful antiviral agent strongly induced upon viral infections 44 . High concentrations of nitric oxide may cause protein nitration resulting in protein dysfunction, as already described in case of cell adhesion molecules subsequently downregulated in endothelial cells after infection 45 . Nitration and subsequent degradation may thus also account for the presently observed downregulation of cell adhesion molecules JUP and CHL1.…”

A hybrid cartilage extracellular matrix-based hydrogel/poly (ε-caprolactone) scaffold incorporated with Kartogenin for cartilage tissue engineering

“…Our results also demonstrated that the hydrogel modification with β-CD essentially does not have any significant effect on cellular proliferation, which is in line with the previously published articles that indicate β-CD is not toxic to cells. [93][94][95] On day 7, the unmodified hydrogel had slightly less viability than the modified hydrogel, but the data still confirms that the hydrogel modification does not induce any cellular toxicity. The results illustrate that a 3D hydrogel environment can provide a favorable environment for both cell growth and cell viability.…”

Oligosaccharides as Potential Therapeutics against Atherosclerosis

“…Firstly, βCD was found to regulate NO production in bovine aortic endothelial cells by inactivating the protein kinase Cε (PKCε), which is known to dephosphorylate T495 in endothelial nitric oxide synthetase (eNOS) ( Figure 2 ). Furthermore, the elevated NO level inhibited IκB degradation, and the subsequent TNFα-induced nuclear factor kappa B (NFκB) activation, thus blocking ICAM-1 and VCAM-1 expression, and thereby inhibiting monocyte adhesion to ECs ( Table 1 ) [ 49 ]. Secondly, another mechanism has been identified on oxLDL and LPS treated HUVECs, whereby MβCD reduced by 2–3 times the expression of ICAM-1 and VCAM-1 , acting through the IKK-NFκB (for LPS) or Akt-NFκB (for oxLDL) pathway [ 50 ].…”