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

Rheumatology (Oxford) 2016 Nov 13;55(11):2056-2065. Epub 2016 Jul 13.

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK

Objective: To test the hypothesis that miR-155 regulates monocyte migratory potential via modulation of chemokine and chemokine receptor expression in RA, and thereby is associated with disease activity.

Methods: The miR-155 copy-numbers in monocytes from peripheral blood (PB) of healthy (n = 22), RA (n = 24) and RA SF (n = 11) were assessed by real time-PCR using synthetic miR-155 as a 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 Taqman low-density arrays 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, the miR-155 copy-number was higher in RA, peripheral blood (PB) and SF monocytes (PB P < 0.01, and SF P < 0.0001). The miR-155 copy-number in RA PB monocytes was higher in ACPA-positive compared with ACPA-negative patients (P = 0.033) and correlated (95% CI) with DAS28 (ESR), R = 0.728 (0.460, 0.874), and 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 and CCL8; upregulated CCR7 expression; and downregulated CCR2. Conversely, miR155 monocytes showed downregulated CCR7 and upregulated CCR2 expression.

Conclusion: 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.

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Source
http://dx.doi.org/10.1093/rheumatology/kew272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088623PMC
November 2016
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