Kurowska-Stolarska, M; Alivernini, S; Ballantine, L E; Asquith, D L; Millar, N L; Gilchrist, D S; Reilly, J; Ierna, M; Fraser, A R; Stolarski, B; McSharry, C; Hueber, A J; Baxter, D; Hunter, J; Gay, S; Liew, F Y; McInnes, I B (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 (PNAS), 108(27):11193-11198.
Full text not available from this repository.
View at publisher
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.
0 downloads since deposited on 12 Jul 2011
0 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine|
|DDC:||610 Medicine & health|
|Deposited On:||12 Jul 2011 12:37|
|Last Modified:||27 Nov 2013 23:33|
|Publisher:||National Academy of Sciences|
|Free access at:||Publisher DOI. An embargo period may apply.|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page