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Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis.

Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis.

Authors :
Pullerits R
Bokarewa M
Jonsson IM
Verdrengh M
Tarkowski A
Source :
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2005 Jan; Vol. 44 (1), pp. 32-9. Date of Electronic Publication: 2004 Sep 14.
Publication Year :
2005

Abstract

Objectives: The aim of the study was to assess the role of extracellular cytochrome c as an inducer of joint inflammation and to examine its levels in sera and synovial fluids of rheumatoid arthritis (RA) patients.<br />Methods: Mice were injected intra-articularly with different doses of cytochrome c and joints were evaluated histopathologically and immunohistochemically 3 and 10 days later. In addition, mouse spleen cells were stimulated with different concentrations of cytochrome c, followed by assessment of NF-kappaB activation and cytokine production. Sera and synovial fluid from RA patients and sera from healthy individuals were assessed with respect to cytochrome c levels by an enzyme-linked immunoassay technique.<br />Results: Histopathological signs of arthritis were evident in 75% of animals following intra-articular injection of cytochrome c. Synovitis was characterized by influx of Mac-1+ cells. In vivo depletion of neutrophils and monocytes led to abrogation of arthritis. Stimulation of mouse spleen cells in vitro with cytochrome c resulted in activation of NF-kappaB and release of proinflammatory cytokines and chemokines. Cytochrome c levels in RA patients' sera were significantly lower than in healthy controls. Further, cytochrome c levels in synovial fluid were significantly lower than in corresponding blood samples.<br />Conclusions: Our findings demonstrate that extracellular cytochrome c displays direct proinflammatory properties mediated by activation of NF-kappaB and causing neutrophil and monocyte triggered inflammation. We hypothesize that decreased levels of cytochrome c in RA patients reflect consumption of this molecule in the synovial tissue, decreasing apoptosis and shifting the balance towards inflammation.

Details

Language :
English
ISSN :
1462-0324
Volume :
44
Issue :
1
Database :
MEDLINE
Journal :
Rheumatology (Oxford, England)
Publication Type :
Academic Journal
Accession number :
15367748
Full Text :
https://doi.org/10.1093/rheumatology/keh406