Abstract
Vascular inflammation plays a key role in the pathogenesis and progression of atherosclerosis, a main complication of diabetes. The present study investigated whether an aqueous extract of Portulaca oleracea (AP) prevents the TNF-α-induced vascular inflammatory process in the human umbilical vein endothelial cell (HUVEC). The stimulation of TNF-α induced overexpression of adhesion molecules affects vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1 and E-selectin for example. However, AP significantly suppressed TNF-α-induced over-expression of these adhesion molecules in a dose-dependent manner. In addition, pretreatment with AP dose-dependently reduced an increase of the adhesion of HL-60 cells to TNF-α-induced HUVEC. Furthermore, we observed that stimulation of TNF-α significantly increased intracellular reactive oxygen species (ROS) production. However, pretreatment with AP markedly blocked TNF-α-induced ROS production in a dose-dependent manner. The western blot and immunofluorescence analysis showed that AP inhibited the translocation of p65 NF-κB to the nucleus. In addition, AP suppressed the TNF-α-induced degradation of IκB-α and attenuated the TNF-α-induced NF-κB binding. AP also effectively reduced TNF-α-induced mRNA expressions of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 in a dose-dependent manner. Taken together, AP prevents the vascular inflammatory process through the inhibition of intracellular ROS production and NF-κB activation as well as the reduction of adhesion molecule expression in TNF-α-induced HUVEC. These results suggested that AP might have a potential therapeutic effect by inhibiting the vascular inflammation process in vascular diseases such as atherosclerosis.
Highlights
Recent investigations of atherosclerosis have focused on vascular inflammation, providing novel insight into mechanisms of disease
Previous studies have shown that Nuclear factor κB (NF-κB) activation is required for the up-regulation of adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, which are responsible for monocyte adhesion and increased vascular inflammation [8,9]
The major finding of this study indicated that pretreatment with AP significantly suppressed the tumor necrosis factor (TNF)-α-induced intracellular reactive oxygen species (ROS) production and up-regulation of adhesion molecules in human umbilical vein endothelial cell (HUVEC) by inhibiting the NF-κB signaling pathway
Summary
Recent investigations of atherosclerosis have focused on vascular inflammation, providing novel insight into mechanisms of disease. Previous studies have indicated that cytokines such as TNF-α change the shape and motility of endothelial cells, which could contribute to vascular leakage at the site of inflammation and that such cytokines stimulate an increase in the expression of cell adhesion molecules [5,6]. Previous studies have shown that NF-κB activation is required for the up-regulation of adhesion molecules such as ICAM-1 and VCAM-1, which are responsible for monocyte adhesion and increased vascular inflammation [8,9]. ROS may serve as a common intracellular messenger for various redox-sensitive transcription pathways that induce adhesion molecule expression in vascular endothelial cells [2,11]. We investigated the anti-vascular inflammatory effect and molecular mechanism of AP in the TNF-α-induced vascular inflammation process in primary cultured human umbilical vein endothelial cells (HUVEC)
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