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Abstract: Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNFα-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNFα-induced production of intracellular reactive oxygen species (ROS) and activation of NF-κB by preventing IκB degradation and inhibiting IκB kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-κB activation, and cell adhesion molecule expression in endothelial cells. [Copyright &y& Elsevier]

Abstract: Methoxychlor (MXC) is a pesticide that was developed as a replacement for dichlorodiphenyltrichloroethane. The influence of MXC on cytokine production or the functions of macrophages is unclear. This study examined the effects of MXC on the production of nitric oxide (NO) and the proinflammatory cytokines (IL-1β, IL-6, and TNF-α), and analyzed the molecular mechanism in mouse macrophages. The addition of MXC to macrophages induced the production of NO and proinflammatory cytokines and expression levels of these genes in a dose-dependent manner. The NF-κB sites were identified in the promoter of the iNOS and proinflammatory cytokines genes. The transient expression and electrophoretic mobility shift assays revealed that the NF-κB transcription factor mediated the MXC-induced increase in the iNOS and proinflammatory cytokines expression levels. In addition, MXC induced the rapid phosphorylation of the ERK1/2 and p38 MAPK. This demonstrates that MXC stimulates the production of NO and proinflammatory cytokines and can up-regulate the expression levels of these genes via NF-κB transactivation and ERK1/2 and p38 MAPK phosphorylation. Overall, this study provides evidence showing that MXC has inflammatory potential that is previously unrecognized immunomodulating activity. [Copyright &y& Elsevier]