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Departments of Immunology and Rheumatology, Hôpital Edouard Herriot and Laboratoire d’ Immuno-Virologie Unité Mixte de Recherche, Centre National de la Recherche Scientifique (CNRS) 5537, Faculté de Médecine Laennec, Lyon;
Schering-Plough Laboratory for Immunological Research, Dardilly; and
CNRS Unité de Recherche Associée (URA) 1456, Université de Bordeaux II, Bordeaux, France
IL-17 is a cytokine produced by CD4 T cells that activates the production of inflammatory mediators by synoviocytes. To study the contribution of soluble factors in the interaction between T cells and synoviocytes in rheumatoid arthritis (RA), we looked at the effect of IL-17 on these cells in the presence of cytokines classified as pro (IL-1)- and anti-inflammatory (IL-4, IL-13, IL-10). Both human rIL-1ß and rIL-17 induced IL-6 and leukemia inhibitory factor (LIF) production by synovial fibroblasts in a dose-dependent manner. After 7 days of culture, optimal concentrations of IL-1ß increased IL-6 (33-fold) and LIF (10-fold) production by synoviocytes, while IL-17 showed a lesser effect on IL-6 (17-fold) and LIF (4-fold) production. Using low concentrations of IL-17 and IL-1ß in combination, a synergistic effect was observed on the production of IL-6, whereas an additive effect was observed for LIF production. Production of biologically active IL-17 was demonstrated in RA synovium supernatants with the use of a blocking anti-IL-17 Ab. Both IL-4 and IL-13 had a modest stimulatory effect on IL-1- and IL-17-induced production of IL-6, but inhibited that of LIF. In contrast, IL-10 had a limited inhibitory effect on IL-6 production and no effect on that of LIF. These findings indicate that low levels of cytokines produced by monocytes (IL-1) and T cells (IL-17) can act together on synoviocytes. Thus, some RA synovium T cells producing IL-17 can activate mesenchymal cells leading to an increased proinflammatory pattern sensitive to Th2 cytokine regulation.
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E. Lubberts, L. van den Bersselaar, B. Oppers-Walgreen, P. Schwarzenberger, C. J. J. Coenen-de Roo, J. K. Kolls, L. A. B. Joosten, and W. B. van den Berg IL-17 Promotes Bone Erosion in Murine Collagen-Induced Arthritis Through Loss of the Receptor Activator of NF-{kappa}B Ligand/Osteoprotegerin Balance J. Immunol., March 1, 2003; 170(5): 2655 - 2662. [Abstract] [Full Text] [PDF]
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S. Ferretti, O. Bonneau, G. R. Dubois, C. E. Jones, and A. Trifilieff IL-17, Produced by Lymphocytes and Neutrophils, Is Necessary for Lipopolysaccharide-Induced Airway Neutrophilia: IL-15 as a Possible Trigger J. Immunol., February 15, 2003; 170(4): 2106 - 2112. [Abstract] [Full Text] [PDF]
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S. Aggarwal, N. Ghilardi, M.-H. Xie, F. J. de Sauvage, and A. L. Gurney Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17 J. Biol. Chem., January 10, 2003; 278(3): 1910 - 1914. [Abstract] [Full Text] [PDF]
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R L van Bezooijen, L van der Wee-Pals, S E Papapoulos, and C W G M Lowik Interleukin 17 synergises with tumour necrosis factor {alpha} to induce cartilage destruction in vitro Ann Rheum Dis, October 1, 2002; 61(10): 870 - 876. [Abstract] [Full Text] [PDF]
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P J Koshy, N Henderson, C Logan, P F Life, T E Cawston, and A D Rowan Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines Ann Rheum Dis, August 1, 2002; 61(8): 704 - 713. [Abstract] [Full Text] [PDF]
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G Chevrel, P Garnero, and P Miossec Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor {alpha} soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3{alpha} and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation Ann Rheum Dis, August 1, 2002; 61(8): 730 - 733. [Abstract] [Full Text] [PDF]
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S. D. Hurst, T. Muchamuel, D. M. Gorman, J. M. Gilbert, T. Clifford, S. Kwan, S. Menon, B. Seymour, C. Jackson, T. T. Kung, et al. New IL-17 Family Members Promote Th1 or Th2 Responses in the Lung: In Vivo Function of the Novel Cytokine IL-25 J. Immunol., July 1, 2002; 169(1): 443 - 453. [Abstract] [Full Text] [PDF]
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 K. Hata, A. Andoh, M. Shimada, S. Fujino, S. Bamba, Y. Araki, T. Okuno, Y. Fujiyama, and T. Bamba IL-17 stimulates inflammatory responses via NF-kappa B and MAP kinase pathways in human colonic myofibroblasts Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G1035 - G1044. [Abstract] [Full Text] [PDF]
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F. Benchetrit, A. Ciree, V. Vives, G. Warnier, A. Gey, C. Sautes-Fridman, F. Fossiez, N. Haicheur, W. H. Fridman, and E. Tartour Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism Blood, March 15, 2002; 99(6): 2114 - 2121. [Abstract] [Full Text] [PDF]
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M. Shimada, A. Andoh, K. Hata, K. Tasaki, Y. Araki, Y. Fujiyama, and T. Bamba IL-6 Secretion by Human Pancreatic Periacinar Myofibroblasts in Response to Inflammatory Mediators J. Immunol., January 15, 2002; 168(2): 861 - 868. [Abstract] [Full Text] [PDF]
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S. Aggarwal and A. L. Gurney IL-17: prototype member of an emerging cytokine family J. Leukoc. Biol., January 1, 2002; 71(1): 1 - 8. [Abstract] [Full Text] [PDF]
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A. Yamashita, Y. Yonemitsu, S. Okano, K. Nakagawa, Y. Nakashima, T. Irisa, Y. Iwamoto, Y. Nagai, M. Hasegawa, and K. Sueishi Fibroblast Growth Factor-2 Determines Severity of Joint Disease in Adjuvant-Induced Arthritis in Rats J. Immunol., January 1, 2002; 168(1): 450 - 457. [Abstract] [Full Text] [PDF]
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M. Chabaud, G. Page, and P. Miossec Enhancing Effect of IL-1, IL-17, and TNF-{alpha} on Macrophage Inflammatory Protein-3{alpha} Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines J. Immunol., November 15, 2001; 167(10): 6015 - 6020. [Abstract] [Full Text] [PDF]
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 P. Ye, F. H. Rodriguez, S. Kanaly, K. L. Stocking, J. Schurr, P. Schwarzenberger, P. Oliver, W. Huang, P. Zhang, J. Zhang, et al. Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense J. Exp. Med., August 20, 2001; 194(4): 519 - 528. [Abstract] [Full Text] [PDF]
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E. Lubberts, L. A. B. Joosten, B. Oppers, L. van den Bersselaar, C. J. J. Coenen-de Roo, J. K. Kolls, P. Schwarzenberger, F. A. J. van de Loo, and W. B. van den Berg IL-1-Independent Role of IL-17 in Synovial Inflammation and Joint Destruction During Collagen-Induced Arthritis J. Immunol., July 15, 2001; 167(2): 1004 - 1013. [Abstract] [Full Text] [PDF]
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Y. Yamamura, R. Gupta, Y. Morita, X. He, R. Pai, J. Endres, A. Freiberg, K. Chung, and D. A. Fox Effector Function of Resting T Cells: Activation of Synovial Fibroblasts J. Immunol., February 15, 2001; 166(4): 2270 - 2275. [Abstract] [Full Text] [PDF]
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C. Infante-Duarte, H. F. Horton, M. C. Byrne, and T. Kamradt Microbial Lipopeptides Induce the Production of IL-17 in Th Cells J. Immunol., December 1, 2000; 165(11): 6107 - 6115. [Abstract] [Full Text] [PDF]
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J. Witowski, K. Pawlaczyk, A. Breborowicz, A. Scheuren, M. Kuzlan-Pawlaczyk, J. Wisniewska, A. Polubinska, H. Friess, G. M. Gahl, U. Frei, et al. IL-17 Stimulates Intraperitoneal Neutrophil Infiltration Through the Release of GRO{alpha} Chemokine from Mesothelial Cells J. Immunol., November 15, 2000; 165(10): 5814 - 5821. [Abstract] [Full Text] [PDF]
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F. Luzza, T. Parrello, G. Monteleone, L. Sebkova, M. Romano, R. Zarrilli, M. Imeneo, and F. Pallone Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa J. Immunol., November 1, 2000; 165(9): 5332 - 5337. [Abstract] [Full Text] [PDF]
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J. Dudler, N. Renggli-Zulliger, N. Busso, M. Lotz, and A. So Effect of interleukin 17 on proteoglycan degradation in murine knee joints Ann Rheum Dis, July 1, 2000; 59(7): 529 - 532. [Abstract] [Full Text]
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R. Schwandner, K. Yamaguchi, and Z. Cao Requirement of Tumor Necrosis Factor Receptor-Associated Factor (Traf)6 in Interleukin 17 Signal Transduction J. Exp. Med., April 3, 2000; 191(7): 1233 - 1240. [Abstract] [Full Text] [PDF]
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M. Ziolkowska, A. Koc, G. Luszczykiewicz, K. Ksiezopolska-Pietrzak, E. Klimczak, H. Chwalinska-Sadowska, and W. Maslinski High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism J. Immunol., March 1, 2000; 164(5): 2832 - 2838. [Abstract] [Full Text] [PDF]
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T. Aarvak, M. Chabaud, P. Miossec, and J. B. Natvig IL-17 Is Produced by Some Proinflammatory Th1/Th0 Cells But Not by Th2 Cells J. Immunol., February 1, 1999; 162(3): 1246 - 1251. [Abstract] [Full Text] [PDF]
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M. A. Antonysamy, W. C. Fanslow, F. Fu, W. Li, S. Qian, A. B. Troutt, and A. W. Thomson Evidence for a Role of IL-17 in Organ Allograft Rejection: IL-17 Promotes the Functional Differentiation of Dendritic Cell Progenitors J. Immunol., January 1, 1999; 162(1): 577 - 584. [Abstract] [Full Text] [PDF]
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Y. Shi, S. J. Ullrich, J. Zhang, K. Connolly, K. J. Grzegorzewski, M. C. Barber, W. Wang, K. Wathen, V. Hodge, C. L. Fisher, et al. A Novel Cytokine Receptor-Ligand Pair. IDENTIFICATION, MOLECULAR CHARACTERIZATION, AND IN VIVO IMMUNOMODULATORY ACTIVITY J. Biol. Chem., June 16, 2000; 275(25): 19167 - 19176. [Abstract] [Full Text] [PDF]
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