Kurowska-Stolarska, M. et al. (2011) MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proceedings of the National Academy of Sciences of the United States of America, 108(27), pp. 11193-11198. (doi: 10.1073/pnas.1019536108) (PMID:21690378)
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Publisher's URL: http://dx.doi.org/10.1073/pnas.1019536108
Abstract
MicroRNA (miRNA) species (miR) regulate mRNA translation and are implicated as mediators of disease pathology via coordinated regulation of molecular effector pathways. Unraveling miR disease-related activities will facilitate future therapeutic interventions. miR-155 recently has been identified with critical immune regulatory functions. Although detected in articular tissues, the functional role of miR-155 in inflammatory arthritis has not been defined. We report here that miR-155 is up-regulated in synovial membrane and synovial fluid (SF) macrophages from patients with rheumatoid arthritis (RA). The increased expression of miR-155 in SF CD14+ cells was associated with lower expression of the miR-155 target, Src homology 2-containing inositol phosphatase-1 (SHIP-1), an inhibitor of inflammation. Similarly, SHIP-1 expression was decreased in CD68+ cells in the synovial lining layer in RA patients as compared with osteoarthritis patients. Overexpression of miR-155 in PB CD14+ cells led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines. Conversely, inhibition of miR-155 in RA synovial CD14+ cells reduced TNF-α production. Finally, miR-155–deficient mice are resistant to collagen-induced arthritis, with profound suppression of antigen-specific Th17 cell and autoantibody responses and markedly reduced articular inflammation. Our data therefore identify a role of miR-155 in clinical and experimental arthritis and suggest that miR-155 may be an intriguing therapeutic target.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Liew, Prof Foo and Reilly, Mr James and Fraser, Dr Alasdair and Asquith, Dr Darren and Gilchrist, Dr Derek and Millar, Professor Neal and Hueber, Dr Axel and Kurowska-Stolarska, Professor Mariola and McSharry, Dr Charles and Alivernini, Mr Stefano |
Authors: | Kurowska-Stolarska, M., Alivernini, S., Ballantine, L., Asquith, D. L., Millar, N. L., Gilchrist, D. S., Reilly, J. H., Ierna, M., Fraser, A. R., Stolarski, B., McSharry, C., Hueber, A. J., Baxter, D., Hunter, J., Gay, S., Liew, F. Y., and McInnes, I. B. |
Subjects: | R Medicine > R Medicine (General) |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
ISSN (Online): | 1091-6490 |
Published Online: | 20 June 2011 |
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