IL-1-induced nitric oxide inhibits chondrocyte proliferation via PGE2.
IL-1 inhibits chondrocyte proliferation induced by TGF beta or serum. This study analyzed the role of nitric oxide (NO), which is induced at high levels by IL-1 in chondrocytes. NO, when administered through sodium nitroprusside (SNP), inhibited TGF beta or serum-induced chondrocyte proliferation. To determine whether IL-1-induced NO is responsible for growth inhibition by IL-1, chondrocytes were cultured in the presence of the nitric oxide synthase inhibitor N-monomethyl-L-arginine (NMA), which dose-dependently reduced the antiproliferative effects of IL-1. Analysis of interactions between PGE2, a known chondrocyte growth inhibitor, and NO showed that PGE2 does not induce NO and is not required for NO induction by IL-1. However, SNP induced high levels of PGE2, and NMA reduced IL-1-induced PGE2. This raised the possibility that PGE2 is a downstream mediator of the antiproliferative effects of NO. This was confirmed in experiments where the growth inhibitory effects of SNP were reduced by indomethacin. These results suggest that the chondrocyte growth inhibition by IL-1 in chondrocytes is due to the induction of NO, which stimulates the production of PGE2 as a mediator of its antiproliferative effects.
Blanco
F J
FJ
Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093, USA.
Lotz
M
M
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D003470:Culture Media; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015232:Dinoprostone; D013936:Thymidine; D007213:Indomethacin