MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis

Elmesmari, A., Fraser, A. R., Wood, C., Gilchrist, D., Vaughan, D., Stewart, L., McSharry, C., McInnes, I. B. and Kurowska-Stolarska, M. (2016) MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis. Rheumatology, 55(11), pp. 2056-2065. (doi:10.1093/rheumatology/kew272) (PMID:27411480) (PMCID:PMC5088623)

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Abstract

Objectives: To test the hypothesis that miR-155 regulates monocyte migratory potential via modulation of chemokine and chemokine receptor expression in rheumatoid arthritis (RA); and thereby is associated with disease activity. Methods: miR-155 copy-number in monocytes from peripheral blood (PB) of healthy (n=22), RA (n=24), and RA synovial fluid (SF; n=11) were assessed by real time- PCR using synthetic miR-155 as quantitative standard. To evaluate the functional impact of miR-155, human monocytes were transfected with control or miR-155 mimic and the effect on transcript levels, and production of chemokines was evaluated by TLDA and multiplex assays. A comparative study evaluated constitutive chemokine receptor expression in miR-155-/- and wild-type murine (CD115+Ly6C+Ly6G-) monocytes. Results: Compared with healthy monocytes, miR-155 copy-number was higher in RA PB and SF monocytes (PB p<0.01, and SF p<0.0001). MiR-155 copy-number in RA PB monocytes were higher in ACPA positive compared with ACPA negative patients (p=0.033) and correlated (95% C.I.) with DAS28 (ESR), R=0.728 (0.460, 0.874), with tender, R=0.631 (0.306, 0.824) and swollen, R=0.503 (0.125, 0.753) joint counts. Enforced-expression of miR-155 in RA monocytes stimulated the production of CCL3, CCL4, CCL5, CCL8; up-regulated CCR7 expression and down-regulated CCR2. Conversely, miR155-/- monocytes showed down-regulated CCR7 and upregulated CCR2 expression. Conclusions: Given the observed correlations with disease activity, these data provide strong evidence that miR-155 can contribute to RA pathogenesis by regulating chemokine production and pro-inflammatory chemokine receptor expression, thereby promoting inflammatory cell recruitment and retention in the RA synovium.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Fraser, Dr Alasdair and Elmesmari, Dr Aziza and Gilchrist, Dr Derek and Wood, Dr Claire and Stewart, Ms Lynn and Kurowska-Stolarska, Dr Mariola and Vaughan, Ms Diane and McSharry, Dr Charles
Authors: Elmesmari, A., Fraser, A. R., Wood, C., Gilchrist, D., Vaughan, D., Stewart, L., McSharry, C., McInnes, I. B., and Kurowska-Stolarska, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Rheumatology
Publisher:Oxford University Press
ISSN:1462-0324
ISSN (Online):1462-0332
Published Online:13 July 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Rheumatology 55(11): 2056-2065
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514111MicroRNA in monocytes: its contribution to the pathogenesis of arthritis and cardiovascular co-morbidityMariola Kurowska-StolarskaArthritis Research UK (ARC)19213III -IMMUNOLOGY