MicroRNA-155 contributes to enhanced resistance to apoptosis in monocytes from patients with rheumatoid arthritis. 2017

Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
Centre for Inflammation Biology and Cancer Immunology, Division of Immunology, Infection and Inflammatory Disease, King's College London, United Kingdom.

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.

UI MeSH Term Description Entries
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001172 Arthritis, Rheumatoid A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. Rheumatoid Arthritis
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D016130 Immunophenotyping Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry. Lymphocyte Immunophenotyping,Lymphocyte Subtyping,Immunologic Subtyping,Immunologic Subtypings,Lymphocyte Phenotyping,Subtyping, Immunologic,Subtypings, Immunologic,Immunophenotyping, Lymphocyte,Immunophenotypings,Immunophenotypings, Lymphocyte,Lymphocyte Immunophenotypings,Lymphocyte Phenotypings,Lymphocyte Subtypings,Phenotyping, Lymphocyte,Phenotypings, Lymphocyte,Subtyping, Lymphocyte,Subtypings, Lymphocyte
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine

Related Publications

Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
November 2017, International journal of rheumatic diseases,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
December 2019, Apoptosis : an international journal on programmed cell death,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
March 1986, Arthritis and rheumatism,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
June 2014, Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
August 1987, British journal of rheumatology,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
January 2022, Frontiers in immunology,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
July 1985, Annals of the rheumatic diseases,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
October 2011, Annals of the rheumatic diseases,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
June 2015, Annals of the rheumatic diseases,
Megha Rajasekhar, and Anton M Olsson, and Kathryn J A Steel, and Mirella Georgouli, and Ushan Ranasinghe, and Christine Brender Read, and Klaus S Frederiksen, and Leonie S Taams
June 2012, Arthritis and rheumatism,
Copied contents to your clipboard!