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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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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. |
format | Online Article Text |
id | pubmed-5088623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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