Glucosamine modulates IL-1-induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF-kappa B pathway.
We recently reported that glucosamine reversed the decrease in proteoglycan synthesis and in UDP-glucuronosyltransferase I mRNA expression induced by interleukin-1 beta (IL-1 beta) [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-1 beta 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-1 beta or with ROS decreased the activation of the nuclear factor kappa B, but not the activator protein-1. After treatment with IL-1 beta, glucosamine increased the expression of mRNA encoding the type II IL-1 beta receptor. These results emphasize the potential role of two regulating proteins of the IL-1 beta signaling pathway that could account for the beneficial effect of glucosamine in osteoarthritis.
Gouze
J N
JN
UMR 7561, CNRS-Université Henri Poincaré-Nancy I, Physiopathologie et Pharmacologie Articulaires, Faculté de Médecine, Vandoeuvre-lès-Nancy, France.
Bianchi
A
A
Bécuwe
P
P
Dauça
M
M
Netter
P
P
Magdalou
J
J
Terlain
B
B
Bordji
K
K
D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005944:Glucosamine / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D053574:Receptors, Interleukin-1 Type II; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
D007375:Interleukin-1; D016328:NF-kappa B; D011509:Proteoglycans; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D018808:Transcription Factor AP-1; C067806:glucuronyltransferase GlcAT-1; D014453:Glucuronosyltransferase; D005944:Glucosamine