N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes

Glucosamine represents one of the most commonly used drugs to treat osteoar thritis. However, mechanisms of its antiarthritic activities are still poor ly understood. The present study identifies a novel mechanism of glucosamin e-mediated anti-inflammatory activity. It is shown that both glucosamine an d N-acetylglucosamine inhibit IL-1 beta- and TNF-a-induced NO production in normal human articular chondrocytes. The effect of the sugars on NO produc tion is specific, since several other monosaccharides, including glucose, g lucuronic acid, and N-acetylmannosamine, do not express this activity. Furt hermore, N-acetylglucosamine polymers, including the dimer and the trimer, also do not affect NO production. The observed suppression of IL-1 beta -in duced NO production Is associated with inhibition of inducible NO synthase mRNA and protein expression. In addition, N-acetylglucosamine also suppress es the production of IL-1 beta -induced cyclooxygenase-2 and IL-6. The cons titutively expressed cyclooxygenase-1, however, was not affected by the sug ar. N-acetylglucosamine-mediated inhibition of the IL-1 beta response of hu man chondrocytes was not associated with the decreased inhibition of the mi togen-activated protein kinases c-Jun N-terminal kinase, extracellular sign al-related kinase, and p38, nor with activation of the transcription factor NF-KB. In conclusion, these results demonstrate that N-acetylglucosamine e xpresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes. The Journal of Immunology, 2001.