Nitric oxide sustains nuclear factor kappaB activation in cytokine-stimulated chondrocytes
In the current studies we have examined the effects of nitric oxide, and its redox derivatives peroxynitrite and S-nitrosothiol, S-nitrosocysteine, on nuclear factor kappaB (NF-κB) activation in cytokine-stimulated bovine chondrocytes. The kinetics of NF-κB activation (p65 nuclear translocation) wer...
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Published in | Osteoarthritis and cartilage Vol. 12; no. 7; pp. 552 - 558 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.07.2004
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Subjects | |
Online Access | Get full text |
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Summary: | In the current studies we have examined the effects of nitric oxide, and its redox derivatives peroxynitrite and
S-nitrosothiol,
S-nitrosocysteine, on nuclear factor kappaB (NF-κB) activation in cytokine-stimulated bovine chondrocytes.
The kinetics of NF-κB activation (p65 nuclear translocation) were assessed by immunofluorescence and immunoblot assays.
We observed that the two nitric oxide redox species, peroxynitrite and
S-nitrosocysteine, exert opposing effects on NF-κB activation. However, in lipopolysaccharide (LPS)/cytokine-stimulated chondrocytes (LPS, IL-1β and TNF-α (LIT)) in the presence or absence of the NOS inhibitor
l-NG-monomethyl arginine citrate (
l-NMMA), the results indicate that nitric oxide causes persistent activation of NF-κB, most likely via generation of the free radical derivative peroxynitrite.
The studies indicate that while nitric oxide is not required for immediate NF-κB activation in cytokine-stimulated chondrocytes, its effect is to sustain nuclear translocation of p65 and thereby provide a persistent “on signal” to NF-κB dependent gene transcription. Persistent activation of NF-κB may represent a mechanism by which nitric oxide sustains catabolic processes and promotes cartilage degeneration in osteoarthritis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1063-4584 1522-9653 |
DOI: | 10.1016/j.joca.2004.04.003 |