ND: |
ME12681956 |
PMID: |
12681956 |
LR: |
20061115 |
CED: |
20030408 |
DCO: |
20030512 |
Autoren: |
Largo R; Alvarez-Soria MA; Díez-Ortego I; Calvo E; Sánchez-Pernaute O; Egido J; Herrero-Beaumont G |
Titel: |
Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes. |
Quelle: |
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society; VOL: 11 (4); p. 290-8 /200304/ |
PM: |
Print |
SU: |
IM |
Sprache: |
English |
CY: |
England |
JID: |
9305697 |
ISSN: |
1063-4584 |
Institution: |
Inflammation Research Unit, Fundación Jiménez Díaz, Autonoma University, Madrid, Spain. |
DT: |
Journal Article; Research Support, Non-U.S. Gov't |
Schlagwörter |
CT: |
ACETYLGLUCOSAMINE/pharmacology; BLOTTING, WESTERN/methods; CARTILAGE, ARTICULAR/*drug effects; CARTILAGE, ARTICULAR/metabolism; CELLS, CULTURED; CHONDROCYTES/*drug effects; CHONDROCYTES/metabolism; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; DINOPROSTONE/biosynthesis; ELECTROPHORETIC MOBILITY SHIFT ASSAY/methods; FLUORESCENT ANTIBODY TECHNIQUE/methods; GALACTOSAMINE/pharmacology; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GLUCOSAMINE/*pharmacology; HUMANS; INTERLEUKIN-1/*metabolism; ISOENZYMES/biosynthesis; MEMBRANE PROTEINS; NF-KAPPA B/*metabolism; OSTEOARTHRITIS, KNEE/*metabolism; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES/biosynthesis |
CTG: |
ACETYLGLUCOSAMIN/Pharmakologie; BLOTTING, WESTERN/Methoden; KNORPEL, GELENK-/*Arzneimittelwirkungen; KNORPEL, GELENK-/Stoffwechsel; ZELLEN, KULTIVIERTE; CHONDROZYTEN/*Arzneimittelwirkungen; CHONDROZYTEN/Stoffwechsel; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; DINOPROSTON/Biosynthese; ELEKTROPHORETISCHER MOBILITY-SHIFT-ASSAY/Methoden; FLUORESZENZ-ANTIKÖRPERTECHNIK/Methoden; GALACTOSAMIN/Pharmakologie; GENEXPRESSIONSREGULATION, ENZYMATISCHE; GLUCOSAMIN/*Pharmakologie; MENSCH; INTERLEUKIN-1/*Stoffwechsel; ISOENZYME/Biosynthese; MEMBRANPROTEINE; NF-KAPPA B/*Stoffwechsel; OSTEOARTHROSE, KNIE/*Stoffwechsel; PROSTAGLANDIN-ENDOPEROXID-SYNTHASE/Biosynthese |
TE: |
Interleukin-1; Isoenzymes; Membrane Proteins; NF-kappa B; Glucosamine/3416-24-8; Dinoprostone/363-24-6; Acetylglucosamine/7512-17-6; Galactosamine/7535-00-4; Cyclooxygenase 1/E.C. 1.14.99.1; Cyclooxygenase 2/E.C. 1.14.99.1; PTGS1 protein, human/E.C. 1.14.99.1; PTGS2 protein, human/E.C. 1.14.99.1; Prostaglandin-Endoperoxide Synthases/E.C. 1.14.99.1 |
CR: |
3416-24-8; 363-24-6; 7512-17-6; 7535-00-4; E.C. 1.14.99.1; E.C. 1.14.99.1; E.C. 1.14.99.1; E.C. 1.14.99.1; E.C. 1.14.99.1 |
AB: |
OBJECTIVE: Glucosamine sulfate (GS) is a commonly used drug for the treatment of osteoarthritis. The mechanism of the action of this drug does, however, remain to be elucidated. In human osteoarthritic chondrocytes (HOC) stimulated with a proinflammatory cytokine, we studied whether GS could modify the NFkappaB activity and the expression of COX-2, a NFkappaB-dependent gene. METHODS: Using HOC in culture stimulated with interleukin-1 beta (IL-1beta), the effects of GS on NFkappaB activation, nuclear translocation of NFkappaB/Rel family members, COX-1 and COX-2 expressions and syntheses and prostaglandin E2 (PGE2) concentration were studied. RESULTS: GS significantly inhibited NFkappaB activity in a dose-dependent manner, as well as the nuclear translocation of p50 and p65 proteins. Furthermore, GS-preincubated IL-1beta-stimulated HOC showed an increase in IkappaBalpha in the cell cytoplasm in comparison with HOC incubated with IL-1beta alone. GS also inhibited the gene expression and the protein synthesis of COX-2 induced by IL-1beta, while no effect on COX-1 synthesis was seen. GS also inhibited the release of PGE2 to conditioned media of HOC stimulated with IL-1beta. CONCLUSIONS: GS inhibits the synthesis of proinflammatory mediators in HOC stimulated with IL-1beta through a NFkappaB-dependent mechanism. Our study further supports the role of GS as a symptom- and structure-modifying drug in the treatment of OA. |