N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes.
Glucosamine represents one of the most commonly used drugs to treat osteoarthritis. However, mechanisms of its antiarthritic activities are still poorly understood. The present study identifies a novel mechanism of glucosamine-mediated anti-inflammatory activity. It is shown that both glucosamine and N-acetylglucosamine inhibit IL-1beta- and TNF-alpha-induced NO production in normal human articular chondrocytes. The effect of the sugars on NO production is specific, since several other monosaccharides, including glucose, glucuronic acid, and N-acetylmannosamine, do not express this activity. Furthermore, N-acetylglucosamine polymers, including the dimer and the trimer, also do not affect NO production. The observed suppression of IL-1beta-induced NO production is associated with inhibition of inducible NO synthase mRNA and protein expression. In addition, N-acetylglucosamine also suppresses the production of IL-1beta-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. N-acetylglucosamine-mediated inhibition of the IL-1beta response of human chondrocytes was not associated with the decreased inhibition of the mitogen-activated protein kinases c-Jun N-terminal kinase, extracellular signal-related kinase, and p38, nor with activation of the transcription factor NF-kappaB. In conclusion, these results demonstrate that N-acetylglucosamine expresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes.
Shikhman
A R
AR
Division of Rheumatology, Scripps Clinic, La Jolla, CA 92037, USA.
Kuhn
K
K
Alaaeddine
N
N
Lotz
M
M
D000116:Acetylgalactosamine / Q000494:pharmacology; D000117:Acetylglucosamine / Q000494:pharmacology*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004789:Enzyme Activation / Q000187:drug effects; D005944:Glucosamine / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000116:Acetylgalactosamine; D005944:Glucosamine; D000117:Acetylglucosamine