Modulation of TNF-α-induced endothelial cell activation by glucosamine, a naturally occurring amino monosaccharide

Atherosclerosis is now considered a chronic inflammatory disease. and glucosamine has the potential to exhibit all anti-inflammatory action. Thus, We investigated the effect Of glucosamine on tumor necrosis factor alpha (TNF-alpha)-induced endothelial cell activation. Human umbilical vein endothelial cells (HUVECs) were Stimulated by TNF-alpha in the presence or absence Of glucosamine or its analogue, N-acetylglucosamine. mRNA expression of MCP-1 (a chemoattractant protein) and ICAM-1 (an adhesion molecule) was evaluated by real-time RT-PCR. and their protein levels were analyzed by ELISA and Western blotting, respectively. Furthermore. the effects of glucosamine oil the phosphorylation of p38MAPK and NF-kappa B, and O-N-acetylglucosamine (O-GlcNAc) modification Were evaluated by Western blotting. The results demonstrated that glucosamine but not N-acetylglucosamine suppressed TNF-alpha-induced expression of MCP-1 and ICAM-1 at both the mRNA and protein levels. Furthermore, glucosamine abrogated the phosphorylation of p38MAPK and NF-kappa B. To note. glucosamine induced O-GlcNAc modification, which was negatively correlated with the expression of MCP-1 and ICAM-1, and phosphorylation of p38MAPK and NF-kappa B. Thus. glucosamine is likely to suppress endothelial cell activation (TNF-alpha-induced ICAM-1 and MCP-1 expression) possibly by affecting p38MAPK and NF-kappa B signaling via O-GlcNAc modification.