Abstract
Survivin belongs to the family of inhibitor of apoptosis proteins and plays an important role in the hyperplastic growth of tissues and tumors. In this study, we assessed the expression of survivin in rheumatoid synovial fluids (SF) and synovial tissues (ST) of rheumatoid arthritis (RA) patients in order to investigate the role of extracellular survivin in the pathogenesis of RA. The survivin level from SF was significantly higher in RA patients (n = 38) than in osteoarthritis patients (n = 18; 10.68 ± 2.76 vs. 1.0 ± 0.56 pg/ml, p = 0.02). In addition, SF survivin level was higher in erosive RA patients (n = 23) than in non-erosive RA patients (n = 15; 15.26 ± 4.26 vs. 4.47 ± 1.12 pg/ml, p = 0.05). SF survivin level in RA was positively correlated with disease activity score 28, but did not reach statistical significance (r = 0.309, p = 0.07). RA SF survivin level was also positively correlated with peripheral blood leukocyte counts (r = 0.443, p = 0.005). The immunohistochemical staining and Western blot analysis revealed survivin expression in the ST and fibroblast-like synoviocytes of RA patients, respectively. These findings suggest that extracellular survivin may be produced from rheumatoid FLS and may play an important role in the destructive RA process.
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Bresnihan, B., P.P. Tak, P. Emery, L. Klareskog, and F. Breedveld. 2000. Synovial biopsy in arthritis research: five years of concerted European collaboration. Annals of the Rheumatic Diseases 59: 506–511.
Firestein, G.S. 1996. Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors? Arthritis and Rheumatism 39: 1781–1790.
Baier, A., I. Meineckel, S. Gay, and T. Pap. 2003. Apoptosis in rheumatoid arthritis. Current Opinion in Rheumatology 15: 274–279.
Andersen, M.H., I.M. Svane, J.C. Becker, and P.T. Straten. 2007. The universal character of the tumor-associated antigen survivin. Clinical Cancer Research 13: 5991–5994.
Li, F., and X. Ling. 2006. Survivin study: an update of "what is the next wave"? Journal of Cellular Physiology 208: 476–486.
Bokarewa, M., S. Lindblad, D. Bokarew, and A. Tarkowski. 2005. Balance between survivin, a key member of the apoptosis inhibitor family, and its specific antibodies determines erosivity in rheumatoid arthritis. Arthritis Res Ther 7: R349–R358.
Mera, S., M. Magnusson, A. Tarkowski, and M. Bokarewa. 2008. Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern. Journal of Leukocyte Biology 83: 149–155.
Galeotti, L., K. Adrian, S. Berg, A. Tarkowski, and M. Bokarewa. 2008. Circulating survivin indicates severe course of juvenile idiopathic arthritis. Clinical and Experimental Rheumatology 26: 373–378.
Park, M.C., S.J. Chung, Y.B. Park, and S.K. Lee. 2008. Relationship of angiogenic factors to disease activity and radiographic damage in rheumatoid arthritis. Clinical and Experimental Rheumatology 26: 881–886.
Arnett, F.C., S.M. Edworthy, D.A. Bloch, D.J. McShane, J.F. Fries, N.S. Cooper, L.A. Healey, S.R. Kaplan, M.H. Liang, H.S. Luthra, et al. 1988. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis and Rheumatism 31: 315–324.
Ahn, J.K., H. Kim, J. Lee, E.K. Bae, H.S. Cha, and E.M. Koh. 2008. Phenotypic characterization and invasive properties of synovial fluid-derived adherent cells in rheumatoid arthritis. Inflammation 31: 365–371.
Stebulis, J.A., R.G. Rossetti, F.J. Atez, and R.B. Zurier. 2005. Fibroblast-like synovial cells derived from synovial fluid. Journal of Rheumatology 32: 301–306.
Deveraux, Q.L., and J.C. Reed. 1999. IAP family proteins—suppressors of apoptosis. Genes and Development 13: 239–252.
Fortugno, P., N.R. Wall, A. Giodini, D.S. O'Connor, J. Plescia, K.M. Padgett, S. Tognin, P.C. Marchisio, and D.C. Altieri. 2002. Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function. Journal of Cell Science 115: 575–585.
Khan, S., J.R. Aspe, M.G. Asumen, F. Almaguel, O. Odumosu, S. Acevedo-Martinez, M. De Leon, W.H. Langridge, and N.R. Wall. 2009. Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. British Journal of Cancer 100: 1073–1086.
Mita, A.C., M.M. Mita, S.T. Nawrocki, and F.J. Giles. 2008. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clinical Cancer Research 14: 5000–5005.
Altieri, D.C. 2003. Validating survivin as a cancer therapeutic target. Nature Reviews Cancer 3: 46–54.
Pope, R.M. 2002. Apoptosis as a therapeutic tool in rheumatoid arthritis. Nature Reviews Immunology 2: 527–535.
Baran, M., L.N. Mollers, S. Andersson, I.M. Jonsson, A.K. Ekwall, J. Bjersing, A. Tarkowski, and M. Bokarewa. 2009. Survivin is an essential mediator of arthritis interacting with urokinase signalling. J Cell Mol Med 13: 3797–3808.
Dharmapatni, A.A., M.D. Smith, D.M. Findlay, C.A. Holding, A. Evdokiou, M.J. Ahern, H. Weedon, P. Chen, G. Screaton, X.N. Xu, and D.R. Haynes. 2009. Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium. Arthritis Res Ther 11: R13.
McInnes, I.B., and G. Schett. 2007. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunology 7: 429–442.
Quehenberger, O. 2005. Thematic review series: the immune system and atherogenesis. Molecular mechanisms regulating monocyte recruitment in atherosclerosis. Journal of Lipid Research 46: 1582–1590.
Tucker, G.C. 2006. Integrins: molecular targets in cancer therapy. Current Oncology Reports 8: 96–103.
Hanashi, M., T. Hayashi, and T. Saito. 2005. Expression of survivin in synovium and cartilage in DBA/1 J mice with type II collagen-induced arthritis. Clinical and Experimental Rheumatology 23: 550.
Ritchlin, C. 2000. Fibroblast biology. Effector signals released by the synovial fibroblast in arthritis. Arthritis Research 2: 356–360.
Salmon, M., D. Scheel-Toellner, A.P. Huissoon, D. Pilling, N. Shamsadeen, H. Hyde, A.D. D'Angeac, P.A. Bacon, P. Emery, and A.N. Akbar. 1997. Inhibition of T cell apoptosis in the rheumatoid synovium. Journal of Clinical Investigation 99: 439–446.
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This work was supported by the Korea Science and Engineering Foundation grant (R01-2004-000-11007-0).
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Ahn, J.K., Oh, JM., Lee, J. et al. Increased Extracellular Survivin in the Synovial Fluid of Rheumatoid Arthritis Patients: Fibroblast-like Synoviocytes as a Potential Source of Extracellular Survivin. Inflammation 33, 381–388 (2010). https://doi.org/10.1007/s10753-010-9196-1
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DOI: https://doi.org/10.1007/s10753-010-9196-1