The study shows that glucosamine, a common supplement, can dampen inflammation caused by the antimicrobial peptide LL‑37 in human blood‑vessel cells. It does this by increasing a cellular sugar modification (O‑GlcNAc) that blocks the cells from releasing inflammatory signals (MCP‑1 and ICAM‑1). This suggests glucosamine might help protect blood vessels from inflammation linked to atherosclerosis.

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-acetylglucosamine (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.