DOI QR코드

DOI QR Code

Type II Collagen으로 유도된 관절염에 대한 강활(羌活), 독활(獨活) 배합약물의 억제 효과

Inhibitory Effect of a Decoction Combined with Ostericum koreanum Maxim. and Aralia continentalis Kitagawa on Collagen II-induced Arthritis Mice

  • 윤호석 (상지대학교 한의과대학) ;
  • 이영철 (상지대학교 한의과대학) ;
  • 이장천 (부산대학교 한의학전문대학원)
  • 투고 : 2013.06.02
  • 심사 : 2013.06.11
  • 발행 : 2013.06.30

초록

Objectives : To clarify the anti-arthritic activity of Ostericum koreanum Maxim. (OS) plus Aralia continentalis Kitagawa (AC) in vivo. Methods : All mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with OS plus AC once a day for 7 weeks. Oral administration of OS plus AC (200 or 50 mg/kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/kg), a positive control. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Results : Administration of OS plus AC significantly suppressed the progression of CIA and inhibited the production of TNF-${\alpha}$ and IL-6 in serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with OS plus AC. In conclusion, our results demonstrates that OS plus AC significantly suppressed the progression of CIA and that this action was characterized by the decreased production of IL-6, IFN-${\gamma}$ and collagen II specific antibody in serum, CD3+CD69+ T cells, MHC class II+/CD11c+ (in DLN), CD11b+Gr-1+ cells (in PBMC), CD11b +Gr-1+ cells, B220+/CD23+ (in paw joint). Conclusions : The the levels of IFN-${\gamma}$ in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. In the serum of OS and AC-treated mice, the levels of IgM RA factor were decreased.

키워드

참고문헌

  1. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001;358:903-11. https://doi.org/10.1016/S0140-6736(01)06075-5
  2. Wolfe T, Mitchell DM, Siley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinhksel SM, Cathey MA. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481-94. https://doi.org/10.1002/art.1780370408
  3. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7:429-42. https://doi.org/10.1038/nri2094
  4. Smolen JS, Alethaha D, Koeller M, Weisman MH, Emery P. Rheumatoid therapies for treatment of rheumatoid arthritis Lancet 2007;370:1861-74. https://doi.org/10.1016/S0140-6736(07)60784-3
  5. Firestein GS. Invasive fibroblast-like synoviocytes in rheumatoid arthritis: passive responders or transformed aggressors? Arthritis Rheum 1996;39:1781-90. https://doi.org/10.1002/art.1780391103
  6. 전국한의과대학공동교재편찬위원회. 본초학. 서울:영림사. 2007:159-161, 303-304.
  7. 신민교. 임상본초학. 서울:영림사. 2002:319-322.
  8. 이승혁. 임상약대론. 서울:의성당. 2008:299.
  9. 이도연, 최고야, 윤태숙, 전명숙, 김승주, 야스카와 켄, 유소연, 김호경. 강활과 방풍의 항염증 상승작용에 관한 연구. 대한본초학회지. 2008;23:39-44.
  10. 박희제, 배기상, 김도윤, 서상완, 박경배, 김병진, 송제문, 이경용, 나철, 신병철, 박성주, 송호준, 황성연. LPS로 자극한 RAW264.7세포에서 강활추출물의 염증성세포활성물질의 억제효과. 대한본초학회지. 2008;23:127-34.
  11. Dang NH, Zhang X, Zheng M, Son KH, Chang H W, Kim HP, Bae K, Kang SS. Inhibitory Const ituents against Cyclooxygenases from Aralia c ordata Thunb. Arch Pharm Res. 2005;28:28-33. https://doi.org/10.1007/BF02975131
  12. 김남옥, Collagen II로 유도된 CIA 관절염 생쥐에 대한 가미해동피산의 억제효과. 동의생리병리학회지. 2007;21:1233-42.
  13. 박원태, 정수현, 서일복, 김순종. 진교.위령선.하고초 복합방이 MIA 유발 골관절염 모델에서 중추신경내 통증관련물질에 미치는 영향. 동의생리병리학회지. 2007;21:1483-90.
  14. 이부균. Collagen II-induced Arthritis 생쥐에 대한 杜沖, 續斷 배합약물의 관절염 억제 효과. 상지대 대학원, 2008
  15. 김태영, 가미대강활탕이 콜라겐II로 유발된 생쥐 모델에 미치는 면학적 연구. 대전대 대학원, 2009.
  16. Tran CN, Lundy SK, Fox DA. Synovial biology and T cells in rheumatoid arthritis. Pathophysiology. 2005;12:183-9. https://doi.org/10.1016/j.pathophys.2005.07.005
  17. 김무진, 윤종화, 김경호, 이승덕, 김갑성. 류마티스성 슬관절염의 침구 치료에 관한 문헌 고찰. 대한침구학회지. 2005;22:191-201.
  18. Deng GM, Lenardo M. The role of immune cells and cytokines in the pathogenesis of rheumatoid arthritis. Drug discovery Today: Disease Mechanisms. 2006;3:163-8.
  19. Svensson L, Jirholt J, Holmdahl R, Jansson L. B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exp Immunol. 1998;111:521-6. https://doi.org/10.1046/j.1365-2249.1998.00529.x
  20. Hara T, Jung LK, Bjorndahl JM, Fu SM. Human T cell activation. III. Rapid induction of a phosphorylated 28 kD/32 kD disulfide linked early activation antigen (EA 1) by 12-O-tetradecanoyl phorbol-13- acetate, mitogens, and antigens. J Exp Med. 1986;164:1988-2005. https://doi.org/10.1084/jem.164.6.1988
  21. Cebrian M, Yague E, Rincon M, Lopez-Botet M, de Landazuri MO, Sanchez-Madrid F. Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes. J Exp Med. 1988;168:1621-37. https://doi.org/10.1084/jem.168.5.1621
  22. Testi R, Phillips JH, Lanier LL. Leu 23 induction as an early marker of functional CD3/T cell antigen receptor triggering. Requirement for receptor cross-linking, prolonged elevation of intracellular [Ca++] and stimulation of protein kinase C. J Immunol. 1989;142:1854-60.
  23. Laffon A, Garcia-Vicuna R, Humbria A, Postigo AA, Corbi AL, de Landazuri MO, Sanchez-Madrid F. Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis. J Clin Invest. 1991;88:546-52. https://doi.org/10.1172/JCI115338
  24. Fehervari Z, Sakaguchi S. A paragon of selftolerance: CD25+ CD4+ regulatory T cells and the control of immune responses. Arthritis Res Ther. 2004;6:19-25.
  25. Loughry A, Fairchild S, Athanasou N, Edwards J, Hall FC. Inflammatory arthritis and dermatitis in thymectomized, CD25+ celldepleted adult mice. Rheumatology (Oxford). 2005;44:299-308. https://doi.org/10.1093/rheumatology/keh477
  26. Morgan ME, Sutmuller RP, Witteveen HJ, van Duivenvoorde LM, Zanelli E, Melief CJ, Snijders A, Offringa R, de Vries RR, Toes RE. CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum. 2003;48:1452-60. https://doi.org/10.1002/art.11063
  27. Lawson CA, Brown AK, Bejarano V, Douglas SH, Burgoyne CH, Greenstein AS, Boylston AW, Emery P, Ponchel F, Isaacs JD. Early rheumatoid arthritis is associated with a deficit in the CD4+CD25 high regulatory T cell population in peripheral blood. Rheumatology (Oxford). 2006;45:1210-7. https://doi.org/10.1093/rheumatology/kel089
  28. van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS. CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum. 2004;50:2775-85. https://doi.org/10.1002/art.20499
  29. Dolhain RJ, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AM. Shift toward T lymphocytes with a T helper 1 cytokinesecretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum. 1996;39:1961-9. https://doi.org/10.1002/art.1780391204
  30. Kadowaki KM, Matsuno H, Tsuji H, Tunru I. CD4+ T cells from collagen-induced arthritic mice are essential to transfer arthritis into severe combined immunodeficient mice. Clin Exp Immunol. 1994;97:212-8.
  31. Williams RO, Whyte A, Waldmann H. Resistance to collagen induced arthritis in DBA/1 mice by intraperitoneal administration of soluble type II collagen involves both CD4+ and CD8+ T lymphocytes. Autoimmunity. 1989;4:237-45. https://doi.org/10.3109/08916938909014700
  32. Bradley DS, Nabozny GH, Cheng S, Zhou P, Griffiths MM, Luthra HS, David CS. HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice: implications in human rheumatoid arthritis. J Clin Invest. 1997;100:2227-34. https://doi.org/10.1172/JCI119760
  33. Gonzalez-Rey E, Chorny A, Varela N, O'Valle F, Delgado M. Therapeutic effect of urocortin on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of regulatory T cells. Arthritis Rheum. 2007;56:531-43. https://doi.org/10.1002/art.22394
  34. Brahn E, Peacock DJ, Banquerigo ML, Liu DY. Effects of tumor necrosis factor alpha (TNF-${\alpha}$) on collagen arthritis. Lymphokine Cytokine Res. 1992;11:253-6.
  35. Furuzawa-Carballeda J, Vargas-Rojas MI, Cabral AR. Autoimmune inflammation from the Th17 perspective. Autoimmun Rev. 2007;6:169-75. https://doi.org/10.1016/j.autrev.2006.10.002
  36. D'Elios M, Del Prete G. Th1/Th2 Balance in Human Disease. Transplant Proc. 1998;30:2373-7. https://doi.org/10.1016/S0041-1345(98)00659-9