[Effect of ginkgolide B on the function of rat aorta smooth cells and U937 cells stimulated by oxLDL].
ABSTRACT To investigate the effect of ginkgolide B on the proliferation of VSMC and the secretion of chemokines by U937 cells stimulated by oxLDL or PAF. In addition, to analyze whether the effect of oxLDL is mediated through PAF receptor.
Using 3H-Tdr incorporation assay, the proliferation of VSMC was measured. The protein and mRNA level of MCP-1 and IL-8 in U937 cells were determined by RT-PCR and ELISA. Using Western blotting the p65 and IkappaB was quantified. The binding of oxLDL to U937 cell was measured by a radio-ligand binding assay of 3H-PAF.
Ginkgolide B inhibited, in dose-dependent manner, the proliferation of VSMC and the secretion of chemokines by U937 cells stimulated by oxLDL, and inhibited the oxLDL-induced p65 activation and depletion of IKappaB. oxLDL inhibited PAF binding to U937 cells.
Ginkgolide B, as a PAF antagonist, possesses the effect of inhibiting the proliferation of VSMC and the secretion of chemokines by U937 cells stimulated by oxLDL in vitro. The effect of oxLDL is, at least in part, mediated through PAF receptor.
SourceAvailable from: Konstantin G Birukov[Show abstract] [Hide abstract]
ABSTRACT: The levels of circulating oxidized phospholipids (OxPLs) become increased in chronic and acute pathologic conditions such as hyperlipidemia, atherosclerosis, increased intimamedia thickness in the patients with systemic Lupus erythematosus, vascular balloon injury, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). These pathologies are associated with inflammation and activation of endothelial cells. Depending on the biological context and the specific group of phospholipid oxidation products, OxPL may exhibit both proinflammatory and anti-inflammatory effects. This review will summarize the data showing a dual role of OxPL in modulation of chronic and acute inflammation as well as OxPL effects on pulmonary endothelial permeability. Recent reports show protective effects of OxPL in the models of endotoxin and ventilator-induced ALI and suggest a potential for using OxPL-derived cyclopenthenone-containing compounds with barrier-protective properties for drug design. These compounds may represent a new group of therapeutic agents for the treatment of lung syndromes associated with acute inflammation and lung vascular leak.Translational Research 05/2009; 153(4):166-76. DOI:10.1016/j.trsl.2008.12.005 · 4.04 Impact Factor