Evaluation of the suppressive actions of glucosamine on the interleukin-1beta-mediated activation of synoviocytes.
OBJECTIVE
Recently, we found that administration of glucosamine to adjuvant arthritis, a model for rheumatoid arthritis, suppressed the progression of arthritis in rats. To clarify its anti-inflammatory mechanism, we evaluated the actions of glucosamine on the activation of synoviocytes in vitro.


METHODS
Synoviocytes isolated from human synovial tissues were stimulated with interleukin (IL)-1beta in the presence of 0.01-1 mM glucosamine. IL-8 and prostaglandin (PG) E(2) were measured by ELISA, and nitric oxide was quantitated by Griess assay. IL-8 mRNA was detected by RT-PCR. Furthermore, the effect of glucosamine on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the binding of [(125)I] IL-1beta to its receptors were examined using a primary human synovial cell line (CSABI- 479).


RESULTS
Glucosamine significantly suppressed the IL-1beta-induced IL-8 production as well as its mRNA expression (p < 0.05) at 1 mM. Furthermore, glucosamine (1 mM) inhibited the IL-1beta-induced nitric oxide and PGE(2) production (p < 0.05). Moreover, glucosamine suppressed the IL-1beta-induced phosphorylation of p38 MAPK (p < 0.05 at >0.1 mM) and the IL-1beta-binding to its receptors (p < 0.05 at 1 mM).


CONCLUSIONS
These observations suggest that glucosamine can suppress the IL-1beta-mediated activation of synoviocytes (such as IL-8-, nitric oxide- and PGE(2)-production, and phosphorylation of p38 MAPK), thereby possibly exhibiting antiinflammatory actions in arthritis.
Hua
J
J
Department of Host Defense and Biochemical Research, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Sakamoto
K
K
Kikukawa
T
T
Abe
C
C
Kurosawa
H
H
Nagaoka
I
I
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D005944:Glucosamine