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Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis.
Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis.
- 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.
- Subjects :
- Adult
Aged
Animals
Arthritis, Experimental pathology
Cells, Cultured
Chemokines biosynthesis
Cytochromes c analysis
Cytochromes c pharmacology
Electrophoretic Mobility Shift Assay
Extracellular Fluid metabolism
Female
Humans
Injections, Intra-Articular
Mice
Mice, Inbred BALB C
Middle Aged
NF-kappa B metabolism
Neutrophils physiology
Spleen cytology
Spleen drug effects
Spleen immunology
Synovial Fluid chemistry
Apoptosis
Arthritis, Experimental chemically induced
Arthritis, Rheumatoid metabolism
Cytochromes c toxicity
Subjects
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