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)

[img]
Preview
Text
118122.pdf - Published Version
Available under License Creative Commons Attribution.

619kB

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 Kurowska-Stolarska, Dr Mariola and Vaughan, Ms Diane and Stewart, Ms Lynn and McSharry, Dr Charles and Gilchrist, Dr Derek and Wood, Dr Claire and Fraser, Dr Alasdair and Elmesmari, Dr Aziza
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

University Staff: Request a correction | Enlighten Editors: Update this record

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