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. 1997 Jun;91(2):252–259. doi: 10.1046/j.1365-2567.1997.00244.x

Inhibitory effects of interleukin-10 on synovial cells of rheumatoid arthritis.

A Kawakami 1, K Eguchi 1, N Matsuoka 1, M Tsuboi 1, S Urayama 1, Y Kawabe 1, T Aoyagi 1, K Maeda 1, S Nagataki 1
PMCID: PMC1363855  PMID: 9227325

Abstract

This paper describes the immunoregulatory effects of interleukin-10 (IL-10) on synovial cells in vitro. Synovial cells were cultured with IL-10 in the presence or absence of various cytokines. Following incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analysed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively. We also examined the effect of IL-10 on the function of synovial cells as antigen-presenting cells (APC). Synovial cells spontaneously express several kinds of costimulatory molecule and produce various kinds of cytokines. Stimulation of synovial cells with interferon-gamma (IFN-gamma), IL-1 beta, or 12-O-tetradecanoyl phorbol 13-acetate (TPA) markedly enhanced the expression of costimulatory molecules and cytokine production of these cells. Both spontaneous and up-regulated costimulatory molecule expression and cytokine production were significantly suppressed by the addition of IL-10. Autologous T-cell proliferation was stimulated by purified protein derivative (PPD) in IFN-gamma-treated synovial cells and treatment of these synovial cells with IL-10 also suppressed T-cell proliferation. Our results suggest that IL-10 has an inhibitory effect on synovial cells and is an important immunoregulatory component of the cytokine network in rheumatoid arthritis.

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Selected References

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  1. Arend W. P., Dayer J. M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990 Mar;33(3):305–315. doi: 10.1002/art.1780330302. [DOI] [PubMed] [Google Scholar]
  2. Azuma M., Ito D., Yagita H., Okumura K., Phillips J. H., Lanier L. L., Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature. 1993 Nov 4;366(6450):76–79. doi: 10.1038/366076a0. [DOI] [PubMed] [Google Scholar]
  3. Böhmig G. A., Kovarik J., Holter W., Pohanka E., Zlabinger G. J. Specific down-regulation of proliferative T cell alloresponsiveness by interference with CD2/LFA-3 and LFA-1/ICAM-1 in vitro. J Immunol. 1994 Apr 15;152(8):3720–3728. [PubMed] [Google Scholar]
  4. Chang C. H., Furue M., Tamaki K. Selective regulation of ICAM-1 and major histocompatibility complex class I and II molecule expression on epidermal Langerhans cells by some of the cytokines released by keratinocytes and T cells. Eur J Immunol. 1994 Nov;24(11):2889–2895. doi: 10.1002/eji.1830241146. [DOI] [PubMed] [Google Scholar]
  5. Chomarat P., Banchereau J., Miossec P. Differential effects of interleukins 10 and 4 on the production of interleukin-6 by blood and synovium monocytes in rheumatoid arthritis. Arthritis Rheum. 1995 Aug;38(8):1046–1054. doi: 10.1002/art.1780380805. [DOI] [PubMed] [Google Scholar]
  6. Cope A. P., Aderka D., Doherty M., Engelmann H., Gibbons D., Jones A. C., Brennan F. M., Maini R. N., Wallach D., Feldmann M. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum. 1992 Oct;35(10):1160–1169. doi: 10.1002/art.1780351008. [DOI] [PubMed] [Google Scholar]
  7. Cush J. J., Splawski J. B., Thomas R., McFarlin J. E., Schulze-Koops H., Davis L. S., Fujita K., Lipsky P. E. Elevated interleukin-10 levels in patients with rheumatoid arthritis. Arthritis Rheum. 1995 Jan;38(1):96–104. doi: 10.1002/art.1780380115. [DOI] [PubMed] [Google Scholar]
  8. Damle N. K., Klussman K., Linsley P. S., Aruffo A. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J Immunol. 1992 Apr 1;148(7):1985–1992. [PubMed] [Google Scholar]
  9. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  10. Dechanet J., Rissoan M. C., Banchereau J., Miossec P. Interleukin 4, but not interleukin 10, regulates the production of inflammation mediators by rheumatoid synoviocytes. Cytokine. 1995 Feb;7(2):176–183. doi: 10.1006/cyto.1995.1024. [DOI] [PubMed] [Google Scholar]
  11. Deleuran B. W., Chu C. Q., Field M., Brennan F. M., Katsikis P., Feldmann M., Maini R. N. Localization of interleukin-1 alpha, type 1 interleukin-1 receptor and interleukin-1 receptor antagonist in the synovial membrane and cartilage/pannus junction in rheumatoid arthritis. Br J Rheumatol. 1992 Dec;31(12):801–809. doi: 10.1093/rheumatology/31.12.801. [DOI] [PubMed] [Google Scholar]
  12. Ding L., Linsley P. S., Huang L. Y., Germain R. N., Shevach E. M. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J Immunol. 1993 Aug 1;151(3):1224–1234. [PubMed] [Google Scholar]
  13. Endo H., Akahoshi T., Takagishi K., Kashiwazaki S., Matsushima K. Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthritis and the induction by IL-8 of leukocyte infiltration and synovitis in rabbit joints. Lymphokine Cytokine Res. 1991 Aug;10(4):245–252. [PubMed] [Google Scholar]
  14. Farahat M. N., Yanni G., Poston R., Panayi G. S. Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 1993 Dec;52(12):870–875. doi: 10.1136/ard.52.12.870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  17. Firestein G. S., Berger A. E., Tracey D. E., Chosay J. G., Chapman D. L., Paine M. M., Yu C., Zvaifler N. J. IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. J Immunol. 1992 Aug 1;149(3):1054–1062. [PubMed] [Google Scholar]
  18. Frei K., Lins H., Schwerdel C., Fontana A. Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. J Immunol. 1994 Mar 15;152(6):2720–2728. [PubMed] [Google Scholar]
  19. Hale L. P., Martin M. E., McCollum D. E., Nunley J. A., Springer T. A., Singer K. H., Haynes B. F. Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment. Arthritis Rheum. 1989 Jan;32(1):22–30. doi: 10.1002/anr.1780320105. [DOI] [PubMed] [Google Scholar]
  20. Harris E. D., Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277–1289. doi: 10.1056/NEJM199005033221805. [DOI] [PubMed] [Google Scholar]
  21. Howard M., O'Garra A. Biological properties of interleukin 10. Immunol Today. 1992 Jun;13(6):198–200. doi: 10.1016/0167-5699(92)90153-X. [DOI] [PubMed] [Google Scholar]
  22. Ihle J. N., Witthuhn B. A., Quelle F. W., Yamamoto K., Thierfelder W. E., Kreider B., Silvennoinen O. Signaling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci. 1994 May;19(5):222–227. doi: 10.1016/0968-0004(94)90026-4. [DOI] [PubMed] [Google Scholar]
  23. Katsikis P. D., Chu C. Q., Brennan F. M., Maini R. N., Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med. 1994 May 1;179(5):1517–1527. doi: 10.1084/jem.179.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Koulova L., Clark E. A., Shu G., Dupont B. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J Exp Med. 1991 Mar 1;173(3):759–762. doi: 10.1084/jem.173.3.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Liu M. F., Kohsaka H., Sakurai H., Azuma M., Okumura K., Saito I., Miyasaka N. The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium. Arthritis Rheum. 1996 Jan;39(1):110–114. doi: 10.1002/art.1780390115. [DOI] [PubMed] [Google Scholar]
  26. Marquardt B., Frith D., Stabel S. Signalling from TPA to MAP kinase requires protein kinase C, raf and MEK: reconstitution of the signalling pathway in vitro. Oncogene. 1994 Nov;9(11):3213–3218. [PubMed] [Google Scholar]
  27. Matsuoka N., Eguchi K., Kawakami A., Ida H., Nakashima M., Sakai M., Terada K., Inoue S., Kawabe Y., Kurata A. Phenotypic characteristics of T cells interacted with synovial cells. J Rheumatol. 1991 Aug;18(8):1137–1142. [PubMed] [Google Scholar]
  28. Matsuoka N., Eguchi K., Kawakami A., Tsuboi M., Kawabe Y., Aoyagi T., Nagataki S. Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells. Clin Exp Immunol. 1996 Jun;104(3):501–508. doi: 10.1046/j.1365-2249.1996.46752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Morales-Ducret J., Wayner E., Elices M. J., Alvaro-Gracia J. M., Zvaifler N. J., Firestein G. S. Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol. 1992 Aug 15;149(4):1424–1431. [PubMed] [Google Scholar]
  30. Stylianou E., O'Neill L. A., Rawlinson L., Edbrooke M. R., Woo P., Saklatvala J. Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes. J Biol Chem. 1992 Aug 5;267(22):15836–15841. [PubMed] [Google Scholar]
  31. Sugiyama E., Kuroda A., Taki H., Ikemoto M., Hori T., Yamashita N., Maruyama M., Kobayashi M. Interleukin 10 cooperates with interleukin 4 to suppress inflammatory cytokine production by freshly prepared adherent rheumatoid synovial cells. J Rheumatol. 1995 Nov;22(11):2020–2026. [PubMed] [Google Scholar]
  32. Taga K., Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol. 1992 Feb 15;148(4):1143–1148. [PubMed] [Google Scholar]
  33. Xu W. D., Firestein G. S., Taetle R., Kaushansky K., Zvaifler N. J. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest. 1989 Mar;83(3):876–882. doi: 10.1172/JCI113971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

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