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

Research output: Contribution to journalArticle

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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 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 (US)
Pages (from-to)3915-3920
Number of pages6
JournalJournal of Immunology
Volume147
Issue number11
StatePublished - Dec 1 1991
Externally publishedYes

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Chondrocytes
Interleukin-1
Lipopolysaccharides
Nitric Oxide
Joints
Cytokines
Dinoprostone
omega-N-Methylarginine
Gelatinases
Fibroblast Growth Factors
Nitrites

ASJC Scopus subject areas

  • Immunology

Cite this

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

Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. / Stadler, Josef; Stefanovic-Racic, Maja; Billiar, Timothy R.; Curran, Ronald D.; Mcintyre, Lori A.; Georgescu, Helga I.; Simmons, Richard L.; Evans, Christopher H.

In: Journal of Immunology, Vol. 147, No. 11, 01.12.1991, p. 3915-3920.

Research output: Contribution to journalArticle

Stadler, J, Stefanovic-Racic, M, Billiar, TR, Curran, RD, Mcintyre, LA, Georgescu, HI, Simmons, RL & Evans, CH 1991, 'Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide', Journal of Immunology, vol. 147, no. 11, pp. 3915-3920.
Stadler J, Stefanovic-Racic M, Billiar TR, Curran RD, Mcintyre LA, Georgescu HI et al. Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. Journal of Immunology. 1991 Dec 1;147(11):3915-3920.
Stadler, Josef ; Stefanovic-Racic, Maja ; Billiar, Timothy R. ; Curran, Ronald D. ; Mcintyre, Lori A. ; Georgescu, Helga I. ; Simmons, Richard L. ; Evans, Christopher H. / Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. In: Journal of Immunology. 1991 ; Vol. 147, No. 11. pp. 3915-3920.
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AU - Mcintyre, Lori A.

AU - Georgescu, Helga I.

AU - Simmons, Richard L.

AU - Evans, Christopher H

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N2 - 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.

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