Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide

Josef Stadler, Maja Stefanovic-Racic, Timothy R. Billiar, Ronald D. Curran, Lori A. Mcintyre, Helga I. Georgescu, Richard L. Simmons, Christopher H. Evans*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

446 Scopus citations


Although IL-1 is an important modulator of chondrocyte metabolism, the postreceptor events triggered by IL-1 remain obscure. The present study shows that IL-1 induces the biosynthesis of nitric oxide (·N=O) by articular chondrocytes. Synthesis of ·N=O is also induced by LPS. Other inflammatory mediators such as IFN-γ, fibroblast growth factor, and TNF-α fail to provoke the production of ·N=O, but they increase the potency of IL-1. A combination of IL-1, LPS, and TNF-α was shown to induce maximal production of 355 ± 51 nmol/106 cells/72 h of nitrite (NO2-), which was measured as a stable end-product of ·N=O generation. The biosynthesis of ·N=O requires an induction period of approximately 6 h and continues for at least 72 h. Inhibition of ·N=O production with the competitive inhibitor NG-monomethyl-L-arginine (NMA) leads to a suppression of gelatinase and PGE2 synthesis by chondrocytes activated with IL-1 alone. In contrast NMA enhances the synthesis of both gelatinase and PGE2 after activation with a combination of IL-1, LPS, and TNF-α. An increase of PGE2 synthesis from 42.0 ± 21.0 to 174.0 ± 33.5 ng/106 cells/72 h resulted from the addition of NMA when these stimulatory agents were combined. Exposure of IL-1 and fibroblast growth factor-stimulated chondrocytes to authentic, exogenous ·N=O led to an increase of PGE2 synthesis from 5.6 ± 1.7 of untreated cells to 15.8 ± 6.8 ng/106 of ·N=O-treated cells within the 1st h. This was followed by a suppression of PGE2 synthesis within the next 2 h.

Original languageEnglish
Pages (from-to)3915-3920
Number of pages6
JournalJournal of Immunology
Issue number11
StatePublished - 1 Dec 1991
Externally publishedYes


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