Luteolin Inhibits Indoxyl Sulfate‐Induced ICAM‐1 and MCP‐1 Expression by Inducing HO‐1 Expression in EA.hy926 Human Endothelial Cells

Abstract

ABSTRACTIn patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti‐inflammatory properties. This study aimed to investigate the effect of luteolin on IS‐mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM‐1) and monocyte chemoattractant protein (MCP‐1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03‐fold, p < 0.05), ICAM‐1 (by 2.19‐fold, p < 0.05) and MCP‐1 protein expression (by 2.18‐fold, p < 0.05), and HL‐60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS‐induced ROS production, ICAM‐1 and MCP‐1 protein expression, and HL‐60 cell adhesion. Moreover, luteolin attenuated IS‐induced nuclear accumulation of p65 and c‐jun. Luteolin dose‐dependently increased heme oxygenase‐1 (HO‐1) expression and the maximum fold induction of HO‐1 by luteolin was 3.68‐fold (p < 0.05), whereas, HO‐1 knockdown abolished the suppression of ICAM‐1 and MCP‐1 expression by luteolin. Luteolin may protect against IS‐induced vessel damage by inducing HO‐1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF‐κB) and activator protein 1 (AP‐1) mediated ICAM‐1 and MCP‐1 expression.