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

Int J Mol Med. 2008 Dec;22(6):809-15.


Atherosclerosis is now considered a chronic inflammatory disease, and glucosamine has the potential to exhibit an 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 on the phosphorylation of p38MAPK and NF-kappaB, 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-kappaB. 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-kappaB. Thus, glucosamine is likely to suppress endothelial cell activation (TNF-alpha-induced ICAM-1 and MCP-1 expression) possibly by affecting p38MAPK and NF-kappaB signaling via O-GlcNAc modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL2 / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Glucosamine / analogs & derivatives
  • Glucosamine / pharmacology*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism*
  • Umbilical Veins / cytology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • CCL2 protein, human
  • Chemokine CCL2
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • p38 Mitogen-Activated Protein Kinases
  • Glucosamine