ND: |
ME11229466 |
PMID: |
11229466 |
LR: |
20061115 |
CED: |
20010302 |
DCO: |
20010322 |
Autoren: |
Gouze JN; Bordji K; Gulberti S; Terlain B; Netter P; Magdalou J; Fournel-Gigleux S; Ouzzine M |
Titel: |
Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. |
Quelle: |
Arthritis and rheumatism; VOL: 44 (2); p. 351-60 /200102/ |
PM: |
Print |
SU: |
AIM IM |
Sprache: |
English |
CY: |
United States |
JID: |
0370605 |
ISSN: |
0004-3591 |
CO: |
ARHEAW |
Institution: |
CNRS-Université Henri Poincaré-Nancy I, Vandoeuvre-lés-Nancy, France. |
DT: |
Journal Article; Research Support, Non-U.S. Gov't |
Schlagwörter |
CT: |
ANIMALS; CELLS, CULTURED; CHONDROCYTES/drug effects; CHONDROCYTES/metabolism; DINOPROSTONE/metabolism; DOWN-REGULATION/drug effects; GLUCOSAMINE/pharmacology; GLUCURONOSYLTRANSFERASE/*biosynthesis; GLUCURONOSYLTRANSFERASE/genetics; GLUCURONOSYLTRANSFERASE/*physiology; GLYCOSAMINOGLYCANS/*biosynthesis; INTERLEUKIN-1/*pharmacology; MALE; MATRIX METALLOPROTEINASE 3/genetics; NITRIC OXIDE/biosynthesis; OSTEOARTHRITIS/drug therapy; RNA, MESSENGER/metabolism; RATS; RATS, WISTAR |
CTG: |
TIER; ZELLEN, KULTIVIERTE; CHONDROZYTEN/Arzneimittelwirkungen; CHONDROZYTEN/Stoffwechsel; DINOPROSTON/Stoffwechsel; DOWN-REGULATION/Arzneimittelwirkungen; GLUCOSAMIN/Pharmakologie; GLUCURONOSYLTRANSFERASE/*Biosynthese; GLUCURONOSYLTRANSFERASE/Genetik; GLUCURONOSYLTRANSFERASE/*Physiologie; GLYCOSAMINO-GLYCANE/*Biosynthese; INTERLEUKIN-1/*Pharmakologie; MÄNNLICH; STROMELYSIN 1/Genetik; STICKSTOFFMONOXID/Biosynthese; OSTEOARTHROSE/Arzneimitteltherapie; RNA, MESSENGER-/Stoffwechsel; RATTUS; RATTEN, WISTAR- |
TE: |
Glycosaminoglycans; Interleukin-1; RNA, Messenger; glucosaminoglycans; Nitric Oxide/10102-43-9; Glucosamine/3416-24-8; Dinoprostone/363-24-6; galactosylgalactoylxylosylprotein 3-beta-glucuronosyltransferase/E.C. 2.4.1.135; Glucuronosyltransferase/E.C. 2.4.1.17; Matrix Metalloproteinase 3/E.C. 3.4.24.17 |
CR: |
10102-43-9; 3416-24-8; 363-24-6; E.C. 2.4.1.135; E.C. 2.4.1.17; E.C. 3.4.24.17 |
AB: |
OBJECTIVE: To assess the variations of galactose-beta-1,3-glucuronosyltransferase I (GlcAT-I) expression related to the decrease in proteoglycan synthesis mediated by interleukin-1beta (IL-1beta) in rat chondrocytes, and to evaluate the influence of glucosamine on the effects elicited by this proinflammatory cytokine. METHODS: Rat articular chondrocytes in primary monolayer cultures or encapsulated into alginate beads were treated with recombinant IL-1beta in the absence or presence (1.0-4.5 gm/liter) of glucosamine. Variations of GlcAT-I and expression of stromelysin 1 (matrix metalloproteinase 3 [MMP-3]) messenger RNA (mRNA) were evaluated by quantitative multistandard reverse transcriptase-polymerase chain reaction. In vitro enzymatic activity of GlcAT-I was measured by thin-layer chromatography, with radiolabeled UDP-glucuronic acid and a digalactoside derivative as substrates. Proteoglycan synthesis was determined by ex vivo incorporation of Na2-35SO4. Nitric oxide synthase and cyclooxygenase activities were monitored by the evaluation of nitrite (NO2-) and prostaglandin E2 (PGE2) produced in the culture medium, respectively. RESULTS: IL-1beta treatment resulted in a marked inhibition of GlcAT-I mRNA expression and in vitro catalytic activity, together with a decrease in proteoglycan synthesis. In addition, glucosamine was able to prevent, in a dose-dependent manner, the inhibitory effects of IL-1beta. In the same way, the amino sugar reduced NO2- and PGE2 production induced by IL-1beta. Finally, the up-regulation of stromelysin 1 (MMP-3) mRNA expression by IL-1beta was fully prevented by glucosamine. CONCLUSION: The results of this study suggest that the deleterious effect of IL-1beta on the anabolism of proteoglycan could involve the repression of GlcAT-I, a key enzyme in the biosynthesis of glycosaminoglycan. Glucosamine was highly effective in preventing these IL-1beta-mediated suppressive effects. The amino sugar also prevented the production of inflammatory mediators induced by the cytokine. This action could account for a possible beneficial effect of glucosamine on osteoarthritic articular cartilage. |