MicroRNA-155 contributes to enhanced resistance to apoptosis in monocytes from patients with rheumatoid arthritis
| Autor: | Rajasekhar, Megha, Olsson, Anton M., Steel, Kathryn J.A., Georgouli, Mirella, Ranasinghe, Ushan, Brender Read, Christine, Frederiksen, Klaus S., Taams, Leonie S. |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Cell death
Cell Survival Immunology Lipopolysaccharide Receptors Apoptosis Microarray Mir-155 Monocyte Article Monocytes Immunophenotyping Arthritis Rheumatoid Immunology and Allergy Humans fas Receptor Gene Expression Profiling Computational Biology Synovial fluid MicroRNAs Gene Ontology Phenotype Gene Expression Regulation Case-Control Studies Cytokines RNA Interference Inflammation Mediators Biomarkers |
| Zdroj: | Rajasekhar, M, Olsson, A M, Steel, K J A, Georgouli, M, Ranasinghe, U, Brender Read, C, Frederiksen, K S & Taams, L S 2017, ' MicroRNA-155 contributes to enhanced resistance to apoptosis in monocytes from patients with rheumatoid arthritis ', Journal of Autoimmunity, vol. 79, pp. 53-62 . https://doi.org/10.1016/j.jaut.2017.01.002 Journal of Autoimmunity |
| Popis: | Monocytes and macrophages are key mediators of inflammation in rheumatoid arthritis (RA). Their persistence at the inflammatory site is likely to contribute to immunopathology. We sought to characterise one mechanism by which persistence may be achieved: resistance to apoptosis and the role of mir-155 in this process. CD14+ monocytes from peripheral blood (PBM) and synovial fluid (SFM) of RA patients were found to be resistant to spontaneous apoptosis relative to PBM from healthy control (HC) individuals. RA SFM were also resistant to anti-Fas-mediated apoptosis and displayed a gene expression profile distinct from HC and RA PBM populations. Gene expression profiling analysis revealed that the differentially expressed genes in RA SFM vs. PBM were enriched for apoptosis-related genes and showed increased expression of the mir-155 precursor BIC. Following identification of potential mir-155 target transcripts by bioinformatic methods, we show increased levels of mature mir-155 expression in RA PBM and SFM vs. HC PBM and a corresponding decrease in SFM of two predicted mir-155-target mRNAs, apoptosis mediators CASP10 and APAF1. Using miR mimics, we demonstrate that mir-155 over-expression in healthy CD14+ cells conferred resistance to spontaneous apoptosis, but not Fas-induced death in these cells, and resulted in increased production of cytokines and chemokines. Collectively our data indicate that CD14+ cells from patients with RA show enhanced resistance to apoptosis, and suggest that an increase in mir-155 may partially contribute to this phenotype. Highlights • CD14+ cells from the inflamed RA joint are strongly resistant to death. • Microarrays show differences in apoptosis genes in CD14+ cells from the RA joint. • Mir-155 is increased and its targets decreased in RA joint CD14+ cells. • Overexpression of mir-155 increases apoptosis resistance of healthy CD14+ cells. |
| Databáze: | OpenAIRE |
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