Modulation of TNF-alpha-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 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.
Ju
Yinghua
Y
Department of Host Defense and Biochemical Research, Juntendo University, School of Medicine, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Hua
Jian
J
Sakamoto
Koji
K
Ogawa
Hideoki
H
Nagaoka
Isao
I
D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; D005944:Glucosamine