Nitric oxide and proteoglycan biosynthesis by human articular chondrocytes in alginate culture.
Interleukin-1 alpha and beta induced the production of large amounts of nitric oxide by normal, human articular chondrocytes in alginate culture; at the same time the biosynthesis of proteoglycan was strongly suppressed. In a dose-dependent manner, NG-monomethyl-L-arginine both inhibited nitric oxide formation and relieved the suppression of proteoglycan synthesis. However concentrations of NG-monomethyl-L-arginine which completely prevented nitric oxide production only partially restored proteoglycan biosynthesis, even at low doses of interleukin-1 where suppression of proteoglycan synthesis was modest. The organic donor of nitric oxide, S-nitrosyl-acetyl-D,L- penicillamine also inhibited proteoglycan biosynthesis, but not as extensively as interleukin-1. These data suggest that interleukin-1 suppresses synthesis of the cartilaginous matrix through more than one mechanism, at least one of which is dependent upon the production of nitric oxide.
Häuselmann
H J
HJ
Department of Rheumatology, University Hospital, Zürich, Switzerland.
Oppliger
L
L
Michel
B A
BA
Stefanovic-Racic
M
M
Evans
C H
CH
D000328:Adult; D000464:Alginates; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D004305:Dose-Response Relationship, Drug; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D012795:Sialoglycoproteins / Q000494:pharmacology; D019323:omega-N-Methylarginine
D000464:Alginates; D006603:Hexuronic Acids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D020723:Glucuronic Acid; D001120:Arginine; D010396:Penicillamine