Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases

Aim： To investigate whether and how COS inhibited IL-8 production in LPS-induced human umbilical vein endothelial cells （HUVECs）. Methods： RT-PCR, enzyme-linked immunosorbent assays （ELISA） and Western blotting were used to study IL-8 expression and related signaling pathway. Wound healing migration assays and monocytic cell adhesion analysis were used to explore the chemotactic and adhesive activities of HUVECs. Results： COS 50-200 μg/mL exerted a significant inhibitory effect on LPS 100 ng/mL-induced IL-8 expression in HUVECs at both the transcriptional and translational levels. In addition, COS 50-200 μg/mL inhibited LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs in a concentration-dependent manner. Signal transduction studies suggest that COS blocked LPS-induced acti- vation of nuclear factor-κB （NF-κB） and activator protein-1 （AP-1） as well as phosphorylation of p38 mitogen-activated protein kinase （MAPK） and phosphokinase Akt. Further, the over-expression of LPS-induced IL-8 mRNA in HUVECs was suppressed by a p38 MAPK inhibitor （SB203580, 25 μmol/L） or a phosphatidylinositol 3-kinase （PI3K） inhibitor （LY294002, 50 pmol/L）. Conclusion： COS inhibited LPS-induced IL-8 expression in HUVECs through the blockade of the p38 MAPK and P13K/Akt signaling path-ways.