류마티스관절염 환자의 활액 세포에서 IL-17과 $IL-1{\beta}$에 의한 IL-23p19의 발현 증가

IL-23 P19 Expression Induced by IL-17 and $IL-1{\beta}$ in Rheumatoid Arthritis Synovial Mononuclear Cells

  • 조미라 (가톨릭대학교 의과대학 류마티스 연구센터) ;
  • 허유정 (가톨릭대학교 의과대학 류마티스 연구센터) ;
  • 오혜좌 (가톨릭대학교 의과대학 류마티스 연구센터) ;
  • 강창민 (가톨릭대학교 의과대학 류마티스 연구센터) ;
  • 이선영 (가톨릭대학교 의과대학 류마티스 연구센터) ;
  • 홍연식 (가톨릭대학교 의과대학 성모자애병원 류마티스내과) ;
  • 김호연 (가톨릭대학교 의과대학 류마티스 연구센터)
  • Cho, Mi-La (Rheumatism Research Center (RhRC), Catholic University) ;
  • Heo, Yu-Jung (Rheumatism Research Center (RhRC), Catholic University) ;
  • Oh, Hye-Jwa (Rheumatism Research Center (RhRC), Catholic University) ;
  • Kang, Chang-Min (Rheumatism Research Center (RhRC), Catholic University) ;
  • Lee, Seon-Yeong (Rheumatism Research Center (RhRC), Catholic University) ;
  • Hong, Yeon-Sik (Departmrnt of Internal Medicine, Our Lady of Mercy Hospital, Catholic University College of Medicine) ;
  • Kim, Ho-Youn (Rheumatism Research Center (RhRC), Catholic University)
  • 발행 : 2008.03.30

초록

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.

키워드

참고문헌

  1. Goldring SR: Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 42;11-16, 2003 https://doi.org/10.1093/oxfordjournals.rheumatology.a005707
  2. Harris ED, Jr: Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322;1277-1289, 1990 https://doi.org/10.1056/NEJM199005033221805
  3. Miossec P: An update on the cytokine network in rheumatoid arthritis. Curr Opin Rheumatol 16;218-222, 2004 https://doi.org/10.1097/00002281-200405000-00009
  4. Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, Miossec P: Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42;963-970, 1999 https://doi.org/10.1002/1529-0131(199905)42:5<963::AID-ANR15>3.0.CO;2-E
  5. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H: Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203;2673-2682, 2006 https://doi.org/10.1084/jem.20061775
  6. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL: Interleukin-23 promotes a distinct CD4T cell activation state characterized by the production of interleukin-17. J Biol Chem 278;1910-1914, 2003 https://doi.org/10.1074/jbc.M207577200
  7. Miossec P: Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum 48;594-601, 2003 https://doi.org/10.1002/art.10816
  8. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441;235-238, 2006 https://doi.org/10.1038/nature04753
  9. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT: Transforming growth factor-beta induces development of the T (H)17 lineage. Nature 441;231-234, 2006 https://doi.org/10.1038/nature04754
  10. Fantini MC, Rizzo A, Fina D, Caruso R, Becker C, Neurath MF, Macdonald TT, Pallone F, Monteleone G: IL-21 regulates experimental colitis by modulating the balance between T (reg) and Th17 cells. Eur J Immunol 37;3155-3163, 2007 https://doi.org/10.1002/eji.200737766
  11. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM: T (H)-17 differentiation: of mice and men. Nat Immunol 8;903-905, 2007 https://doi.org/10.1038/ni0907-903
  12. Kim KW, Cho ML, Park MK, Yoon CH, Park SH, Lee SH, Kim HY: Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor kappaB-dependent pathway in patients with rheumatoid arthritis. Arthritis Res Ther 7;139-148, 2005
  13. Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE, Hromas R: Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol 167;4137-4140, 2001 https://doi.org/10.4049/jimmunol.167.8.4137
  14. Brombacher F, Kastelein RA, Alber G: Novel IL-12 family members shed light on the orchestration of Th1 responses. Trends Immunol 24;207-212, 2003 https://doi.org/10.1016/S1471-4906(03)00067-X
  15. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA: Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13;715-725, 2000 https://doi.org/10.1016/S1074-7613(00)00070-4
  16. Kim W, Min S, Cho M, Youn J, Min J, Lee S, Park S, Cho C, Kim H: The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA). Clin Exp Immunol 119;175-181, 2000 https://doi.org/10.1046/j.1365-2249.2000.01095.x
  17. Wiekowski MT, Leach MW, Evans EW, Sullivan L, Chen SC, Vassileva G, Bazan JF, Gorman DM, Kastelein RA, Narula S, Lira SA: Ubiquitous transgenic expression of the IL-23 subunit P19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol 166;7563-7570, 2001 https://doi.org/10.4049/jimmunol.166.12.7563
  18. Frucht DM: IL-23: a cytokine that acts on memory T cells. Sci STKE 114;PE1, 2002
  19. Belladonna ML, Renauld JC, Bianchi R, Vacca C, Fallarino F, Orabona C, Fioretti MC, Grohmann U, Puccetti P: IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J Immunol 168;5448-5454, 2002 https://doi.org/10.4049/jimmunol.168.11.5448
  20. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW: A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbetal and a novel cytokine receptor subunit. IL-23R. J Immunol 168;5699-5708, 2002 https://doi.org/10.4049/jimmunol.168.11.5699
  21. Broberg EK, Setala N, Eralinna JP, Salmi AA, Roytta M, Hukkanen V: Herpes simplex virus type 1 infection induces upregulation of interleukin-23 (p19) mRNA expression in trigeminal ganglia of BALB/c mice. J Interferon Cytokine Res 22;641-651, 2002 https://doi.org/10.1089/10799900260100123
  22. Zhang Z, Andoh A, Yasui H, Inatomi O, Hata K, Tsujikawa T, Kitoh K, Takayanagi A, Shimizu N, Fujiyama Y: Interleukin-1beta and tumor necrosis factor-alpha upregulate interleukin-23 subunit p19 gene expression in human colonic subepithelial myofibroblasts. Int J Mol Med 15;79-83, 2005
  23. Sheibanie AF, Tadmori I, Jing H, Vassiliou E, Ganea D: Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. FASEB J 18;1318-1320, 2004 https://doi.org/10.1096/fj.03-1367fje
  24. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD: Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421;744-748, 2003 https://doi.org/10.1038/nature01355
  25. Trinchieri G: Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3;133-146, 2003 https://doi.org/10.1038/nri1001
  26. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, Dhodapkar M, Krueger JG: Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 199;125-130, 2004 https://doi.org/10.1084/jem.20030451
  27. Ohshima S, Saeki Y, Mima T, Sasai M, Nishioka K, Nomura S, Kopf M, Katada Y, Tanaka T, Suemura M, Kishimoto T: Interleukin 6 plays a key role in the development of antigen- induced arthritis. Proc Natl Acad Sci USA 95;8222-8226, 1998 https://doi.org/10.1073/pnas.95.14.8222
  28. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ: IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201;233-240, 2005 https://doi.org/10.1084/jem.20041257
  29. Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ: Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med 203; 2473-2483, 2006 https://doi.org/10.1084/jem.20061099
  30. Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hunter CA, Kastelein RA, Cua DJ: Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 116;1317-1326, 2006 https://doi.org/10.1172/JCI25308
  31. Hoy MD, O'Donnell JL, Hart DN: Dual CD45RA, CD45RO positive T-lymphocytes within rheumatoid arthritic joints. Pathology 25;167-173, 1993 https://doi.org/10.3109/00313029309084793
  32. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP: IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 160;3513-3521, 1998
  33. Chabaud M, Page G, Miossec P: Enhancing effect of IL-1, IL-17, and TNF-alpha on macrophage inflammatory protein-3alpha production in rheumatoid arthritis: regulation by soluble receptors and Th2 cytokines. J Immunol 167;6015-6020, 2001 https://doi.org/10.4049/jimmunol.167.10.6015
  34. Kim HR, Cho ML, Kim KW, Juhn JY, Hwang SY, Yoon CH, Park SH, Lee SH, Kim HY: Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF-kappaB- and p38 MAPK-dependent signalling pathways. Rheumatology 46;57-64, 2007 https://doi.org/10.1093/rheumatology/kel159
  35. Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF: The prevalence of knee osteoarthritis in the elderly. The Framingham osteoarthritis study. Arthritis Rheum 30;914-918, 1987 https://doi.org/10.1002/art.1780300811