Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Suppressive Effects of JTT on Collagen-Induced Arthritis in Mice

정통탕(定痛湯)이 콜라젠으로 유도한 관절염 동물 병태 모델에 미치는 효과

  • Cho, Jong-Cheol (Department of Pathology, College of Oriental Medicine, Daejeon University) ;
  • Koo, Young-Sun (Department of Pathology, College of Oriental Medicine, Daejeon University) ;
  • Kim, Dong-Hee (Department of Pathology, College of Oriental Medicine, Daejeon University)
  • 조종철 (대전대학교 한의과대학 병리학교실) ;
  • 구영선 (대전대학교 한의과대학 병리학교실) ;
  • 김동희 (대전대학교 한의과대학 병리학교실)
  • Published : 2007.02.25
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Abstract

Rheumatoid arthritis is an autoimmune disease involving multiple joint. In order to access the suppressive effects of JTT on rheumatoid arthritis and it's effects on immune system we investigated whether JTT could suppress the disease progression of collagen-induced arthritis. DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with DW, JTT (200 or 400 mg/kg) or methotrexate (MTX, 30 mg/kg) as a positive control. Oral administration of JTT significantly suppressed the progression of CIA, which extend is comparable to that of MTX. Histological examination reveled that JTT inhibited infiltration of inflammatory cells into affected paw joint and bone erosion and cartilage destruction were greatly reduced compared with control. Total cell number of spleen, lymph node and peripheral blood were significantly reduced. The absolute number of CD19$^+$, CD3$^+$/CD69$^+$, CD4$^+$/CD25$^+$ cell in spleen from JTT treated mice were significantly decreased. The absolute number of CD19$^+$, CD3$^+$, CD3$^+$/CD69$^+$, CD4$^+$, CD4$^+$/CD25$^+$ CD8$^+$, CD49b, CD3/CD49b cells in draining lymph node were significantly increased compared with control. In peripheral blood mononuclear cells of JTT treated mice, the absolute number of CD4$^+$, CD4$^+$/CD25$^+$, CD3$^+$/CD69$^+$ cells were significantly decreased compared with control, while that of CD49b$^+$ was slightly increased. Infiltration of CD3$^+$ cells and CD11b$^+$/Gr-1$^+$ cells into paw joint was significantly reduced in JTT treated mice. The levels of pathologic cytokines including TNF-a and IL-6 in serum were significantly decreased by oral treatment with JTT The levels of IFN-g in the culture supernatant of splenocyte stimulated with CD3$^+$/CD28$^+$ or collagen were dramatically decreased, while the levels of IL-4 was increased under CD3$^+$/CD28$^+$ or collagen stimulation. Rheumatoid factors including IgG, IgM and collagen specific antibody were present much lower in the serum of JTT treated mice than control. Taken together, JTT has suppressive effects on rheumatoid arthritis by modulating immune system, and has potential to use anti-rheumatic arthritic agent in human.

Keywords

References

  1. Goronzy, J.J. and Weyand, C.M. Rheumatoid arthritis. Immunol Rev, 204:55-73, 2005 https://doi.org/10.1111/j.0105-2896.2005.00245.x
  2. Goldring, S.R., Gravalles, E.M. Pathogenesis of bone erosion in rheumatoid arthritis. Current Opin Rheumatol, 12:195-199, 2002
  3. Carson, D.A., Chen, P.P., Kipps, T. New roles for rheumatoid factor. J Clin Invest, 87:379-383, 1991 https://doi.org/10.1172/JCI115007
  4. Tighe, H., Chen, P.P., Trucker, R. et al. Function of B cells expressing a human immunoglobulin M rheumatoid factor autoantibody in transgenic mic. J Exp Med, 177:109-118, 1993 https://doi.org/10.1084/jem.177.1.109
  5. Weyand, C.M. et al. B cells in rheumatoid synovitis. Arthritis Res Ther, 7(Suppl 3):S9-S12, 2005
  6. Kotake, S. et al. Activated human T cells directly induce osteoclasto- genesis from human monocytes: possible role of T cells in bone destruction in RA patients. Arthritis Rheum, 44:1003-1012, 2001 https://doi.org/10.1002/1529-0131(200105)44:5<1003::AID-ANR179>3.0.CO;2-#
  7. Takemura, S. et al T cell activation in RA is B cell dependent. J Immunol, 167:4710-4718, 2001 https://doi.org/10.4049/jimmunol.167.8.4710
  8. Goronzy, J.J. and Weyand, C.M. T cell regulation in rheumatoid arthritis. Curr Opin Rheumatol, 16:212-217, 2004 https://doi.org/10.1097/00002281-200405000-00008
  9. Kaolowaki, K.M., Matsuno, H., Tsuji, H., Tunru, I. CD4+ T cells from collagen-induced arthritis in mice are essential to transfer arthritis into severe combined immunodeficienct mice. Clin Exp Immunol, 97:212-218, 1994 https://doi.org/10.1111/j.1365-2249.1994.tb06070.x
  10. Kang, Y.M. et al. CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med, 195:1325 -1336, 2002 https://doi.org/10.1084/jem.20011565
  11. Weyand, C.M. et al. Cell-cell interactions in synovitis Interactions between T cells and B cells in rheumatoid arthritis. Arthritis Res, 2:457-463, 2000 https://doi.org/10.1186/ar128
  12. Mor, A. et al. The fibroblast-like synovial cell in rheumatoid arthritis: a key player in inflammtion and joint destruction. Clin Immunol, 115:118-128, 2005 https://doi.org/10.1016/j.clim.2004.12.009
  13. Kraan, M.C. et al. T cells, fibroblast-like synoviocytes and granzyme B+ cytotoxic cells are associated joint damage in patient with recent onset rheumatoid arthritis. Ann Rheum Dis, 63:483-488, 2004 https://doi.org/10.1136/ard.2003.009225
  14. 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
  15. Miossec, P. Pro and anti-inflmmatory cytokine balance in rheumatoid arthritis. Clin Exp Rheumatol, 13(Suppl, 12):S13-S16
  16. Klimiuk, M.C. et al. Production of cytokine and metalloproteinase in rheumatoid arthritis is T cell dependent. Clin Immunol. 90:65-78, 1999 https://doi.org/10.1006/clim.1998.4618
  17. Ponchel, F. et al. Dysregulated lymphocyte proliferation and differen- tiation in patient with rheumatoid arthritis. Blood, 100:4550-4556, 2002 https://doi.org/10.1182/blood-2002-03-0671
  18. 이순보 외. 中醫痰病學. 학원출판사, p 264, 2003
  19. 한주원. 祛濕複合方이 류마토이드 關節炎 치료효과에 대한 실험적 연구. 동의생리병리학회지. 20(5):1241-1244, 2006
  20. 고광재. 생체외 류마토이드 관절염 실험 모델에서 加味靈仙除痛飮의 효과. 원광대학교 대학원, 2003
  21. 김철호 외. 황백 및 위영선 약침이 Lipopolysaccharide 유발관절염의 IL-1${\beta}$ 발현 억제에 미치는 영향. 大韓鍼灸學會誌, 16(1):511-531, 1999
  22. Yoon, Joung Yi Lee, Ji Yun Sim, Sang Soo Kim, Chang Jong. Anti-inflammatory and Analgesic Activity of Fractions of Plantago asiatica Herb. Chung-Ang journal of pharmacal sciences, 17:129-147, 2003
  23. 김영훈. 류마티스양 관절염에 응용되는 방기의 효능에 관한 실험적 연구. 東西醫學, 12(4):37-57, 1987
  24. 최도영 외. 목통 약침자극이 통풍 유발 흰쥐에 미치는 영향. 大韓鍼灸學會誌, 14(2):173-189, 1997
  25. 송인광 외. 전갈 약침이 adjuvant 유발 흰쥐의 관절활액막내 cytokine과 prostaglandin E2에 미치는 영향. 大韓鍼灸學會誌, 19(2):177-188, 2002
  26. Ricardo, T., Paniagua, Orr Sharpe, Peggy P. Ho, Steven M. Chan, Anna Chang, John P. Higgins, Beren H. Tomooka, Fiona M. Thomas, Jason J. Song, Stuart B. Goodman, David M. Lee, Mark C. Genovese, Paul J. Utz, Lawrence Steinman, and William, H. Robinson Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis. J. Clin. Invest., Oct 116:2633-2642, 2006 https://doi.org/10.1172/JCI28546.
  27. Jung Won Moon, Min Suck Oh. Inhibitory effect of Coicis Semen composition on inflammatory responses in the collagen-induced arthritis mouse model. Korean journal Oriental Physiology & Pathology. 20(5):1311-1314, 2006
  28. 곽중문 외. 疎風活血湯加味方이 collagen으로 誘發된 생쥐의 關節炎 억제에 관한 연구. 동의병리학회지, 16(4):810-817, 2002
  29. 서해경 외. 류마토이드 關節炎 患者 滑膜細胞에 대한 鷄血藤의 免疫反應. 동의병리학회지, 17(3):780-786, 2003
  30. 김호철 외. Human Monocyte의 IL-8 생산 억제에 미치는 류마토이드 관절염 치료제로서의 五加皮의 효과. 大韓本草學會誌, 10(1):49-58, 1995
  31. Ingrid Marty, Veronique Peclat, Gailute Kirdaite, Roberto Salvi, Alexa nder So, and Nathalie Busso. Amelioration of collagen-induced arthritis by thrombin inhibition. J. Clin. Invest., 107:631-640, 2001 https://doi.org/10.1172/JCI11064
  32. Morgan, M.E., Sutmuller, R.P.M. et al. CD25+ Cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum, 48:1452-1460, 2003 https://doi.org/10.1002/art.11063
  33. Morgan, M.E., Flierman, R. et al. Effective treatment of collagen induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum, 52:2212-2221, 2005 https://doi.org/10.1002/art.21195
  34. Gavin, Ma, Clarke, S.R., Negrou, E., Gallegos, A. et al. Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat Immunol, 3:33-41, 2002 https://doi.org/10.1038/ni743
  35. Charbonmier, L.M., Duivenvoorde, L.M. and Apparally, F. Immature dendritic cell suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells. J Immunol, 177:3806-3813, 2006 https://doi.org/10.4049/jimmunol.177.6.3806
  36. Werfel, T., Boeker, E. and Kapp, A. Rapid expression of the CD 69 antigen on T cells and natural killer cells upon antigenic stimulation of peripheral blood mononuclear cell suspensions. Allergy, 52:465-469, 1997 https://doi.org/10.1111/j.1398-9995.1997.tb01031.x
  37. Sancho, D,, Gomez, M., Viedma, F., Esplugnes, E., Gordon-Alonson, M. et al. CD 69 down regulates autoimmune reactivity throug active transformin growth factor-beta production in collagen-induced arthritis. J Clin Invest, 112:872-882, 2003 https://doi.org/10.1172/JCI200319112
  38. Sancho, D., Gomez, M., Martines, D.H.G., Lamana, A. et al. CD69 targeting differentially affects the course of collagen-induced arthritis. J Leukoc. Biol, 80:1233-1241, 2006 https://doi.org/10.1189/jlb.1205749
  39. Veena, Taneja and Chella, S., David, H.L.A. Transgenic Mice as Humanized Mouse Models of Disease and Immunity. J. Clin. Invest., 101:921-926, 1998 https://doi.org/10.1172/JCI2860