MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis

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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Professor Foo and Reilly, Mr James and Fraser, Dr Alasdair and Asquith, Dr Darren and Gilchrist, Dr Derek and Hueber, Dr Axel and Millar, Dr Neal and Kurowska-Stolarska, Dr 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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514422Regulation of the adaptive immune response by chemokine scavenging receptorsGerard GrahamMedical Research Council (MRC)G0901113Infection Immunity and Inflammation Medicine
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198III -IMMUNOLOGY