[HTML][HTML] Nitric oxide sustains nuclear factor kappaB activation in cytokine-stimulated chondrocytes
RM Clancy, PF Gomez, SB Abramson - Osteoarthritis and Cartilage, 2004 - Elsevier
RM Clancy, PF Gomez, SB Abramson
Osteoarthritis and Cartilage, 2004•ElsevierOBJECTIVE: 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. METHODS: The kinetics of NF-κB
activation (p65 nuclear translocation) were assessed by immunofluorescence and
immunoblot assays. RESULTS: We observed that the two nitric oxide redox species,
peroxynitrite and S-nitrosocysteine, exert opposing effects on NF-κB activation. However, in …
derivatives peroxynitrite and S-nitrosothiol, S-nitrosocysteine, on nuclear factor kappaB (NF-
κB) activation in cytokine-stimulated bovine chondrocytes. METHODS: The kinetics of NF-κB
activation (p65 nuclear translocation) were assessed by immunofluorescence and
immunoblot assays. RESULTS: We observed that the two nitric oxide redox species,
peroxynitrite and S-nitrosocysteine, exert opposing effects on NF-κB activation. However, in …
OBJECTIVE
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.
METHODS
The kinetics of NF-κB activation (p65 nuclear translocation) were assessed by immunofluorescence and immunoblot assays.
RESULTS
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.
CONCLUSION
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.
Elsevier