Chitosan oligosaccharides inhibit TNF-α-induced VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways

This study aimed to investigate the inhibitive effects of chitosan oligosaccharides (COS) on tumor necrosis factor (TNF)-alpha-induced over-expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs). We found that COS effectively inhibited TNF-alpha-induced expression of VCAM-1 and ICAM-1 at the level of transcription and translation. Signal transduction studies suggested that COS blocked TNF-alpha-induced activation of NF-kappa B, degradation of I kappa B alpha, and phosphorylation of p38 MAPK and ERK1/2. A further investigation showed that the NF-kappa B activation can be partly suppressed by p38 MAPK inhibitor (58203580) and ERK1/2 inhibitor (PD98059), which also ameliorated the mRNA expression of VCAM-1 and ICAM-1 in TNF-alpha-induced HUVECs. Additionally, COS decreased U937 monocyte adhesion to HUVECs induced by TNF-alpha. Our findings suggest that COS inhibit VCAM-1 and ICAM-1 production in activated HUVECs at least partly through the blockade of p38 and ERK1/2 signaling pathways. (C) 2010 Elsevier Ltd. All rights reserved.