Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide

J. Stadler, M. Stefanovic-Racic, T. R. Billiar, R. D. Curran, L. A. McIntyre, H. I. Georgescu, R. L. Simmons, C. H. Evans

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421 Scopus citations

Abstract

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 N(G)- 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 (US)
Pages (from-to)3915-3920
Number of pages6
JournalJournal of Immunology
Volume147
Issue number11
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Stadler, J., Stefanovic-Racic, M., Billiar, T. R., Curran, R. D., McIntyre, L. A., Georgescu, H. I., Simmons, R. L., & Evans, C. H. (1991). Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. Journal of Immunology, 147(11), 3915-3920.