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Neutrophil-derived mitochondrial DNA promotes receptor activator of nuclear factor κB and its ligand signalling in rheumatoid arthritis.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2017 Jul 01; Vol. 56 (7), pp. 1200-1205. - Publication Year :
- 2017
-
Abstract
- Objectives: Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils.<br />Methods: The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry.<br />Results: SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP concentrations. We also showed that mtDNA drives neutrophil RANKL expression to the same extent as Toll-like receptor agonists.<br />Conclusion: Our data identify SF neutrophils as a cellular source of mtDNA that leads to a subsequent expression of RANKL. This highlights the important role of neutrophils in RA osteoimmunology.<br /> (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)
- Subjects :
- Adult
Aged
Arthritis, Rheumatoid immunology
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Humans
Male
Middle Aged
Neutrophils metabolism
Oxidative Stress genetics
Real-Time Polymerase Chain Reaction methods
Reference Values
Retrospective Studies
Signal Transduction genetics
Arthritis, Rheumatoid genetics
DNA, Mitochondrial metabolism
Gene Expression Regulation
RANK Ligand genetics
Receptor Activator of Nuclear Factor-kappa B genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 56
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 28340056
- Full Text :
- https://doi.org/10.1093/rheumatology/kex041