Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by pain, swelling and progressive destruction of synovial joints. The synovial membranes of the affected joints markedly increase in size due to infiltration of several cell types, of which macrophages, lymphocytes and fibroblasts are most abundant. These cell types are activated and release a plethora of inflammatory mediators, such as cytokines, chem-okines and matrix metalloproteinases (MMPs). Synovial membranes can be removed from the joints of RA patients (most commonly when the respective joint is undergoing replacement therapy) and enzymati-cally digested, analyzed or cultured ex vivo. Analysing the cytokine profile of distinct populations of ex vivo RA-patients derived synoviocytes can provide an insight into the pathogenic mechanisms underlying RA. Additionally, since ex vivo cultures of synoviocytes spontaneously produce cytokines they serve as an excellent model for investigating the efficacy of novel anti-inflammatory drugs.
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References
Feldmann, M., Brennan, F.M. and Maini, R.N. (1996) Rheumatoid arthritis. Cell 85, 307–310.
McDowell, T.L., Symons, J.A., Ploski, R., Forre, O. and Duff, G.W. (1995) A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism. Arthritis Rheum 38, 221–228.
Wilson, A.G., de Vries, N., Pociot, F., di Gio-vine, F.S., van der Putte, L.B. and Duff, G.W. (1993) An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med 177, 557–560.
MacGregor, A.J., Fox, H., Ollier, W.E., Snaith, M.L. and Silman, A.J. (1993) An identical twin pair discordant for rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 11, 425–428.
Silman, A.J., MacGregor, A.J., Thomson, W., Hol-ligan, S., Carthy, D., Farhan, A. and Ollier, W.E. (1993) Twin concordance rates for rheumatoid arthritis: results from a nationwide study. Br J Rheumatol 32, 903–907.
Allard, S.A., Muirden, K.D., Camplejohn, K.L. and Maini, R.N. (1987) Chondrocyte-derived cells and matrix at the rheumatoid cartilage-pannus junction identified with monoclonal antibodies. Rheumatol Int 7, 153–159.
Feldmann, M., Brennan, F.M. and Maini, R.N. (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14, 397–440.
Abrahamsen, T.G., Froland, S.S., Natvig, J.B. and Pahle, J. (1975) Elution and characterization of lymphocytes from rheumatoid inflammatory tissue. Scand J Immunol 4, 823–830.
Klareskog L., Forsum, U., Malmnas Tjern-lund, U.K., Kabelitz, D. and Wigren, A. (1981) Appearance of anti-HLA-DR-reac-tive cells in normal and rheumatoid synovial tissue. Scand J Immunol 14, 183–192.
Van Boxel, J.A. and Paget, S.A. (1975) Predominantly T-cell infiltrate in rheumatoid synovial membranes. N Engl J Med 293, 517–520.
Buchan, G., Barrett, K., Turner, M., Chantry, D., Maini, R.N. and Feldmann, M. (1988) Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha. Clin Exp Immunol 73, 449–455.
Field, M., Chu, C., Feldmann, M. and Maini, R.N. (1991) Interleukin-6 localisation in the synovial membrane in rheumatoid arthritis. Rheumatol Int 11, 45–50.
Fontana, A., Hengartner, H., Weber, E., Fehr, K., Grob, P.J. and Cohen, G. (1982) Interleukin 1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheuma-tol Int 2, 49–53.
Brennan, F.M., Chantry, D., Jackson, A., Maini, R. and Feldmann, M. (1989) Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2, 244–247.
Feldmann, M., Brennan, F.M., Elliott, M., Katsikis, P. and Maini, R.N. (1994) TNF alpha as a therapeutic target in rheumatoid arthritis. Circ Shock 43, 179–184.
Elliott, M.J., Maini, R.N., Feldmann, M., Kalden, J.R., Antoni, C., Smolen, J.S., Leeb, B., Breedveld, F.C., Macfarlane, J.D., Bijl, H., et al. (1994) Randomised doubleblind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344, 1105–1110.
Elliott, M.J., Maini, R.N., Feldmann, M., Long-Fox, A., Charles, P. , Katsikis, P. , Bren-nan, F.M., Walker, J., Bijl, H., Ghrayeb, J., et al. (1993) Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 36, 1681–1690.
Maini, R.N., Elliott, M.J., Brennan, F.M., Williams, R.O., Chu, C.Q., Paleolog, E., Charles, P.J., Taylor, P.C. and Feldmann, M. (1995) Monoclonal anti-TNF alpha antibody as a probe of pathogenesis and therapy of rheumatoid disease. Immunol Rev 144, 195–223.
Rankin, E.C., Choy, E.H., Kassimos, D., Kingsley, G.H., Sopwith, A.M., Isenberg, D.A. and Panayi, G.S. (1995) The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis. Br J Rheumatol 34, 334–342.
Feldmann, M. and Maini, R.N. (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19, 163–196.
Acknowledgments
We would like to thank Ms Lauren Scheiwitz and Ms Renee Best (Kennedy Institute) for help with synovial membrane processing and Ms Helen Banks (Kennedy institute) for critical reading of the manuscript. This work was supported by the ARC.
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Thomson, S., Udalova, I.A. (2009). Quantitative Measurement of Cytokine Expression in Synoviocytes Derived from Rheumatoid Arthritis Patients. In: Kozlov, S.V. (eds) Inflammation and Cancer. Methods in Molecular Biology™, vol 512. Humana Press. https://doi.org/10.1007/978-1-60327-530-9_12
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DOI: https://doi.org/10.1007/978-1-60327-530-9_12
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