Glucosamine, a naturally occurring amino monosaccharide modulates LL-37-induced endothelial cell activation

Abstract

Atheroscleros is now considered as a chronic inflammatory disease, and glucosamine has a potential to exhibit anti-inflammatory action. Thus, we investigated the effect of glucosamine on LL-37-induced endothelial cell activation. HUVEC (human umbilical vein endothelial cells) were stimulated by LL-37 in the presence or absence of glucosamine (0.01-1 mM) or its analogue, N-acetyl-glucosamine (0.1-1 mM). mRNA expression of MCP-1 (monocyte chemoattractant protein-1) and ICAM-1 (intercellular adhesion molecule-1) was evaluated by real-time RT-PCR, and their protein levels were analyzed by ELISA and Western blotting, respectively. Furthermore, the effect of glucosamine on O-N-acetylglucosamine (O-GlcNAc) modification was evaluated by Western blotting. Glucosamine but not N-acetylglucosamine suppressed the LL-37-induced expression of MCP-1 and ICAM-1 at both mRNA (p<0.05 at 0.1 mM) and protein levels (p<0.05 at 1 mM). Of interest, O-GlcNAc modification was induced by incubating HUVEC with glucosamine (p<0.05 at 1 mM) but not N-acetylglucosamine. Of note, alloxan, an O-N-acetylglucosamine transferase inhibitor, which prevented the glucosamine-induced O-GlcNAc modification, abrogated the suppressive effect of glucosamine on MCP-1 and ICAM-1 expression (p<0.05 at 0.5 mM). These observations suggest that glucosamine modulates endothelial cell activation possibly via O-GlcNAc modification, and may exhibit an anti-inflammatory action on atherosclerosis.