The role of miR-155 in monocyte migration in Rheumatoid arthritis

Elmesmari, A., Gilchrist, D., Fraser, A., Brewer, J. , McInnes, I. and Kurowska-Stolarska, M. (2012) The role of miR-155 in monocyte migration in Rheumatoid arthritis. In: European Congress of Immunology, Glasgow, UK, 5-8 Sept 2012, pp. 588-589. (doi:10.1111/imm.12002)

Elmesmari, A., Gilchrist, D., Fraser, A., Brewer, J. , McInnes, I. and Kurowska-Stolarska, M. (2012) The role of miR-155 in monocyte migration in Rheumatoid arthritis. In: European Congress of Immunology, Glasgow, UK, 5-8 Sept 2012, pp. 588-589. (doi:10.1111/imm.12002)

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Abstract

Purpose/Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint destruction. The recruitment of effectors cells, including monocytes to the joint space is an important step in RA progression and is mediated by chemokines (Ch) and their receptors (ChR). MicroRNAs are a recently discovered class of posttranscriptional regulators. Many members of the miR family are implicated in the regulation of cell movement and migration. Our previous study showed miR-155 is upregulated in RA synovial fluid (SF) monocytes suggesting that this miR may be involved in activation of these cells, including their migration into joint space. We hypothesized that miR-155 could regulates migration of monocytes in RA by modulating the expression of the chemokine and chemokine receptor system.<p></p> Materials and methods: Peripheral blood (PB) CD14+ cells from healthy controls (HC) and RA patients were transfected with miR-155 mimic or scramble mimic using N-TER nanoparticles and cultured for 48 h. TaQman Low Density Array and multiplex assay was used to evaluate ChR expression and Ch production, respectively. Similar analysis was carried out on bone marrow monocytes (BMM) from miR-155-/- and WT mice. In addition, absolute copy numbers of miR- 155 transcripts in PB and SF CD14+ of RA and HC were assessed by QPCR.<p></p> Results: PB and SF monocytes in RA patients showed higher copy number of miR-155 compared to HC. Overexpression of miR-155 in HC and RA monocytes did not affect the production of CCL2, CCL7, CCL21, CXCL5, CXCL8, CXCL7, CXCL10 and CX3CL1. In contrast, overexpression of miR-155 induced the production of chemokines such as CCL4, CCL5 and CCL22 in RA monocytes and CCL3 in both RA and HC. Analysis of chemokine receptors in BMM of miR-155-/- and WT mice revealed significantly higher levels of CCR1, CCR2, CCR5 and CXCR4 in miR-155 deficient cells suggesting that miR-155 can act as a negative regulator of these receptors in homeostatic state. As expected, TLR-4 ligand significantly suppressed expression of these receptors in both WT and miR-155-/- cells. Analysis of 3’UTRs of Ch/ ChR (TargetScan) suggests that miR-155 is likely interfering with signaling pathways implicated in Ch/ChR system expression. Conclusions: Deregulation of miR-155 in RA monocytes can contribute to the production of pro-inflammatory chemokines by these cells and to their accumulation at sites of inflammation.<p></p>

Item Type:Conference Proceedings
Additional Information:Special Issue: Immunology, 137(Sup 1). pp. 588-589
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Fraser, Dr Alasdair and Elmesmari, Dr Aziza and Brewer, Professor James and Gilchrist, Dr Derek and Kurowska-Stolarska, Dr Mariola
Authors: Elmesmari, A., Gilchrist, D., Fraser, A., Brewer, J., McInnes, I., and Kurowska-Stolarska, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Blackwell Publishing Ltd.
ISSN:0019-2805
ISSN (Online):1365-2567

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