ND: |
ME11290798 |
PMID: |
11290798 |
LR: |
20061115 |
CED: |
20010406 |
DCO: |
20010628 |
Autoren: |
Shikhman AR; Kuhn K; Alaaeddine N; Lotz M |
Titel: |
N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes. |
Quelle: |
Journal of immunology (Baltimore, Md. : 1950); VOL: 166 (8); p. 5155-60 /20010415/ |
PM: |
Print |
SU: |
AIM IM |
Sprache: |
English |
CY: |
United States |
JID: |
2985117R |
ISSN: |
0022-1767 |
CO: |
JOIMA3 |
Institution: |
Division of Rheumatology, Scripps Clinic, La Jolla, CA 92037, USA. |
DT: |
Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
NG: |
AG07996 AG NIA; AT00052 AT NCCAM |
Schlagwörter |
CT: |
ACETYLGALACTOSAMINE/pharmacology; ACETYLGLUCOSAMINE/*pharmacology; ACTIVE TRANSPORT, CELL NUCLEUS/drug effects; ANTI-INFLAMMATORY AGENTS/*pharmacology; CARTILAGE, ARTICULAR/drug effects; CARTILAGE, ARTICULAR/enzymology; CARTILAGE, ARTICULAR/immunology; CARTILAGE, ARTICULAR/metabolism; CELL NUCLEUS/drug effects; CELL NUCLEUS/metabolism; CELLS, CULTURED; CHONDROCYTES/*drug effects; CHONDROCYTES/enzymology; CHONDROCYTES/immunology; CHONDROCYTES/*metabolism; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; ENZYME ACTIVATION/drug effects; GLUCOSAMINE/pharmacology; HUMANS; INTERLEUKIN-1/*antagonists & inhibitors; INTERLEUKIN-1/*physiology; INTERLEUKIN-6/biosynthesis; ISOENZYMES/antagonists & inhibitors; ISOENZYMES/biosynthesis; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MEMBRANE PROTEINS; MITOGEN-ACTIVATED PROTEIN KINASES/metabolism; NF-KAPPA B/metabolism; NITRIC OXIDE/antagonists & inhibitors; NITRIC OXIDE/biosynthesis; NITRIC OXIDE SYNTHASE/antagonists & inhibitors; NITRIC OXIDE SYNTHASE/biosynthesis; NITRIC OXIDE SYNTHASE TYPE II; PHOSPHORYLATION/drug effects; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES/biosynthesis; P38 MITOGEN-ACTIVATED PROTEIN KINASES |
CTG: |
ACETYLGALACTOSAMIN/Pharmakologie; ACETYLGLUCOSAMIN/*Pharmakologie; AKTIVER TRANSPORT, ZELLKERN/Arzneimittelwirkungen; ANTIPHLOGISTIKA/*Pharmakologie; KNORPEL, GELENK-/Arzneimittelwirkungen; KNORPEL, GELENK-/Enzymologie; KNORPEL, GELENK-/Immunologie; KNORPEL, GELENK-/Stoffwechsel; ZELLKERN/Arzneimittelwirkungen; ZELLKERN/Stoffwechsel; ZELLEN, KULTIVIERTE; CHONDROZYTEN/*Arzneimittelwirkungen; CHONDROZYTEN/Enzymologie; CHONDROZYTEN/Immunologie; CHONDROZYTEN/*Stoffwechsel; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; ENZYMAKTIVIERUNG/Arzneimittelwirkungen; GLUCOSAMIN/Pharmakologie; MENSCH; INTERLEUKIN-1/*Antagonisten & Inhibitoren; INTERLEUKIN-1/*Physiologie; INTERLEUKIN-6/Biosynthese; ISOENZYME/Antagonisten & Inhibitoren; ISOENZYME/Biosynthese; JNK-MITOGEN-AKTIVIERTE PROTEINKINASEN; MEMBRANPROTEINE; MITOGENAKTIVIERTE PROTEINKINASEN/Stoffwechsel; NF-KAPPA B/Stoffwechsel; STICKSTOFFMONOXID/Antagonisten & Inhibitoren; STICKSTOFFMONOXID/Biosynthese; STICKSTOFFMONOXID-SYNTHASE/Antagonisten & Inhibitoren; STICKSTOFFMONOXID-SYNTHASE/Biosynthese; STICKSTOFFMONOXID-SYNTHASE TYP II; PHOSPHORYLIERUNG/Arzneimittelwirkungen; PROSTAGLANDIN-ENDOPEROXID-SYNTHASE/Biosynthese; P38-MITOGEN-AKTIVIERTE PROTEINKINASEN |
TE: |
Anti-Inflammatory Agents; Interleukin-1; Interleukin-6; Isoenzymes; Membrane Proteins; NF-kappa B; Nitric Oxide/10102-43-9; Acetylgalactosamine/31022-50-1; Glucosamine/3416-24-8; Acetylglucosamine/7512-17-6; NOS2A protein, human/E.C. 1.14.13.39; Nitric Oxide Synthase/E.C. 1.14.13.39; Nitric Oxide Synthase Type II/E.C. 1.14.13.39; 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; JNK Mitogen-Activated Protein Kinases/E.C. 2.7.1.37; Mitogen-Activated Protein Kinases/E.C. 2.7.1.37; p38 Mitogen-Activated Protein Kinases/E.C. 2.7.1.37 |
CR: |
10102-43-9; 31022-50-1; 3416-24-8; 7512-17-6; E.C. 1.14.13.39; E.C. 1.14.13.39; E.C. 1.14.13.39; 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; E.C. 2.7.1.37; E.C. 2.7.1.37; E.C. 2.7.1.37 |
AB: |
Glucosamine represents one of the most commonly used drugs to treat osteoarthritis. However, mechanisms of its antiarthritic activities are still poorly understood. The present study identifies a novel mechanism of glucosamine-mediated anti-inflammatory activity. It is shown that both glucosamine and N-acetylglucosamine inhibit IL-1beta- and TNF-alpha-induced NO production in normal human articular chondrocytes. The effect of the sugars on NO production is specific, since several other monosaccharides, including glucose, glucuronic acid, and N-acetylmannosamine, do not express this activity. Furthermore, N-acetylglucosamine polymers, including the dimer and the trimer, also do not affect NO production. The observed suppression of IL-1beta-induced NO production is associated with inhibition of inducible NO synthase mRNA and protein expression. In addition, N-acetylglucosamine also suppresses the production of IL-1beta-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. N-acetylglucosamine-mediated inhibition of the IL-1beta response of human chondrocytes was not associated with the decreased inhibition of the mitogen-activated protein kinases c-Jun N-terminal kinase, extracellular signal-related kinase, and p38, nor with activation of the transcription factor NF-kappaB. In conclusion, these results demonstrate that N-acetylglucosamine expresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes. |