Glucosamine modulates IL‐1‐induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF‐κB pathway

Abstract

We recently reported that glucosamine reversed the decrease in proteoglycan synthesis and in UDP-glucuronosyltransferase I mRNA expression induced by interleukin-1L L (IL-1L L) [Arthritis Rheum. 44 (2001) 351^360]. In the present work, we show that glucosamine does not exert the same effects when chondrocytes were stimulated with reactive oxygen species (ROS). In order to better understand its mechanism of action, we determined if glucosamine could prevent the binding of IL-1L L to its cellular receptors or could interfere with its signaling pathway at a post-receptor level. Addition of glucosamine to rat chondrocytes treated with IL-1L L or with ROS decreased the activation of the nuclear factor U UB, but not the activator protein-1. After treatment with IL-1L L, glucosamine increased the expression of mRNA encoding the type II IL-1L L receptor. These results emphasize the potential role of two regulating proteins of the IL-1L L signaling pathway that could account for the beneficial effect of glucosamine in osteoarthritis. ß

Glucosamine Abrogates the Acute Phase of Experimental Autoimmune Encephalomyelitis by Induction of Th2 Response

“…In addition, the potential immunoregulatory capacity of glucosamine has also been suggested. Indeed, glucosamine has been shown to suppress proinflammatory cytokine action in human chondrocytes (10), to inhibit NF-B activation and IL-1␤ bioactivity in rat chondrocytes (11), and to suppress unprimed T cell response by interfering with functions of APCs and by a direct inhibitory effect on CD3-induced T cell proliferation (12). Furthermore, the addition of glucosamine to immune cells in vitro prevented both their activation and their ability to initiate the MLR.…”

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells

“…At the cellular level, GlcN inhibits interleukin-1␤ (IL-1␤)-induced nuclear factor-B (NF-B) activation in chondrocytes (10,11). As well, GlcN inhibits lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages and microglia (10 -14).…”

Application des techniques de thérapie génique aux maladies ostéo-articulaires

“…Ainsi, la surexpression du TGFβ dans la membrane synoviale provoque l'apparition de fibroses pulmonaires massives nécessitant l'euthanasie de l'animal (données personnelles), tandis que le transfert de l'ADNc exprimant BMP2 a été suivi de formations osseuses ectopiques [29]. Une autre approche utilisant l'accumulation intracellulaire de glucosamine semble protéger les cellules contre les effets néfastes de l'IL-1 [30]. La glucosamine est utilisée de façon empirique dans le traitement de l'arthrose, et bien que ce ne soit pas une protéine, son accumulation est rendue possible par la surexpression de la glutamine fructose 6-phosphate-amido-transfé-rase (GFAT), enzyme impliquée dans sa biosynthèse.…”