Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

Abstract

The expression of adhesion molecules in endothelial cells elicited by lipopolysaccharide (LPS) is involved in the adhesive interaction between endothelial cells and monocytes in inflammation. In this study, in order to characterize the anti-inflammatory effects of chitosan oligosaccharides (COS) on LPS-induced inflammation and to elucidate the underlying mechanisms, the mRNA levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were measured in porcine iliac artery endothelial cells (PIECs). When these cells were treated with COS, the LPS-induced mRNA expression of E-selectin and ICAM-1 was reduced through the inhibition of the signal transduction cascade, p38 mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor-?B (NF-?B). Moreover, through the inhibition of p38 MAPK and ERK1/2, COS suppressed the LPS-induced NF-?B p65 translocation. We found that COS suppressed the phosphorylation of p38 MAPK and the translocation of NF-?B p65 into the nucleus in a dose-dependent manner, and inhibited the adhesion of U973 cells to PIECs. Based on these results, it can be concluded that COS downregulate the expression of E-selectin and ICAM-1 by inhibiting the phosphorylation of MAPKs and the activation of NF-?B in LPS-treated PIECs. Our study demonstrates the valuable anti-inflammatory properties of COS.