Evaluation of the suppressive actions of glucosamine on the interleukin-1β-mediated activation of synoviocytes

Objective: Recently, we found that administration of glucosamine to adjuvant arthritis, a model for rheumatoid arthritis, suppressed the progression of arthritis in rats. To clarify its anti-inflammatory mechanism, we evaluated the actions of glucosamine on the activation of synoviocytes in vitro. Materials and methods: Synoviocytes isolated from human synovial tissues were stimulated with interleukin (IL)-1β in the presence of 0.01–1 mM glucosamine. IL-8 and prostaglandin (PG) E₂ were measured by ELISA, and nitric oxide was quantitated by Griess assay. IL-8 mRNA was detected by RT-PCR. Furthermore, the effect of glucosamine on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the binding of ¹²⁵I] IL-1β to its receptors were examined using a primary human synovial cell line (CSABI- 479). Results: Glucosamine significantly suppressed the IL-1β-induced IL-8 production as well as its mRNA expression (p < 0.05) at 1 mM. Furthermore, glucosamine (1 mM) inhibited the IL-1β-induced nitric oxide and PGE₂ production (p < 0.05). Moreover, glucosamine suppressed the IL-1β-induced phosphorylation of p38 MAPK (p < 0.05 at >0.1 mM) and the IL-1β-binding to its receptors (p < 0.05 at 1 mM). Conclusions: These observations suggest that glucosamine can suppress the IL-1β-mediated activation of synoviocytes (such as IL-8-, nitric oxide- and PGE₂-production, and phosphorylation of p38 MAPK), thereby possibly exhibiting antiinflammatory actions in arthritis. Received 5 February 2007; returned for revision 20 March 2007; accepted by M. Katori 8 June 2007