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

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), R...

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Autores principales: Elmesmari, Aziza, Fraser, Alasdair R., Wood, Claire, Gilchrist, Derek, Vaughan, Diane, Stewart, Lynn, McSharry, Charles, McInnes, Iain B., Kurowska-Stolarska, Mariola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088623/
https://www.ncbi.nlm.nih.gov/pubmed/27411480
http://dx.doi.org/10.1093/rheumatology/kew272
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author Elmesmari, Aziza
Fraser, Alasdair R.
Wood, Claire
Gilchrist, Derek
Vaughan, Diane
Stewart, Lynn
McSharry, Charles
McInnes, Iain B.
Kurowska-Stolarska, Mariola
author_facet Elmesmari, Aziza
Fraser, Alasdair R.
Wood, Claire
Gilchrist, Derek
Vaughan, Diane
Stewart, Lynn
McSharry, Charles
McInnes, Iain B.
Kurowska-Stolarska, Mariola
author_sort Elmesmari, Aziza
collection PubMed
description 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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spelling pubmed-50886232016-11-02 MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis Elmesmari, Aziza Fraser, Alasdair R. Wood, Claire Gilchrist, Derek Vaughan, Diane Stewart, Lynn McSharry, Charles McInnes, Iain B. Kurowska-Stolarska, Mariola Rheumatology (Oxford) Basic Science 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. Oxford University Press 2016-11 2016-07-13 /pmc/articles/PMC5088623/ /pubmed/27411480 http://dx.doi.org/10.1093/rheumatology/kew272 Text en © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Science
Elmesmari, Aziza
Fraser, Alasdair R.
Wood, Claire
Gilchrist, Derek
Vaughan, Diane
Stewart, Lynn
McSharry, Charles
McInnes, Iain B.
Kurowska-Stolarska, Mariola
MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis
title MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis
title_full MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis
title_fullStr MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis
title_full_unstemmed MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis
title_short MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis
title_sort microrna-155 regulates monocyte chemokine and chemokine receptor expression in rheumatoid arthritis
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088623/
https://www.ncbi.nlm.nih.gov/pubmed/27411480
http://dx.doi.org/10.1093/rheumatology/kew272
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