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Effects of Red-ginseng Extracts on the Activation of Dendritic Cells

고려홍삼의 수지상세포 활성화 효과

  • 김도순 (순천대학교 생물학과) ;
  • 박정은 (순천대학교 생물학과) ;
  • 서권일 (순천대학교 식품영양학과) ;
  • 고성룡 (KT&G 중앙연구원 인삼과학연구소) ;
  • 이종원 (KT&G 중앙연구원 인삼과학연구소) ;
  • 도재호 (KT&G 중앙연구원 인삼과학연구소) ;
  • 이성태 (순천대학교 생물학과)
  • Published : 2006.09.30

Abstract

Ginseng is a medicinal herb widely used in Asian countries. Dendritic cells(DCs) play a pivotal role in the initiation of T cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. In this study, we examined the effects of Red-ginseng(water extract, edible and fermented ethyl alcohol extract, crude saponin) on the DCs phenotypic and functional maturation. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated by water extract, edible and fermented ethyl alcohol extract, crude saponin and LPS, respectively, for 24hours. The expression of surface co-stimulatory molecules, including MHC(major histocompatibility complex) class II, CD40, CD80 and CD86, was increased on DCs that were stimulated with crude saponin, but antigen-uptake capacity was decreased. The antigen-presenting capacity of Red-ginseng extracts-treated DCs as analyzed by allogeneic T cells proliferation and IL-2, $IFN-{\gamma}$ production was increased. Furthermore, $CD4^+$ and $CD8^+$ syngeneic T cell(OVA-specific) proliferation and $IFN-{\gamma}$ production was significantly increased. However, $CD4^+$ syngeneic T cell secreted higher levels of IL-2 in responding but not $CD8^+$ syngeneic T cell. These results indicate the immunomodulatory properties of Red-ginseng extracts, which might be therapeutically useful in the control of cancers and immunodeficient diseases through the up-regulation of DCs maturation.

본 연구에서는 정관장 홍삼의 물(water) extract, 식용발효 주정 extract 및 홍삼 추출물로부터 분리 제조한 crude saponin을 이용하여 면역반응을 매개하는 수지상세포의 활성 효과에 대하여 알아보았다. 그 결과 홍삼시료 중, crude saponin $100\;{\mu}g/ml$을 처리하였을 때 수지상세포의 세포표면 분자인 MHC class II, CD40, CD80, CD86의 발현이 증가하였으며, phagocytosis는 감소하였다. 또한 홍삼시료를 처리한 수지상세포와 allogeneic T세포를 함께 배양하였을 때, 홍삼시료의 물 extract, 식용발효주정 extract, crude saponin 모두 allogeneic T세포의 증식반응을 유도하였고, IL-2와 $IFN-{\gamma}$의 생산량을 증가시키는 것을 확인하였다. 또한 $CD4^+$ syngeneic T세포와 $CD8^+$ syngeneic T세포의 반응에서도 T세포의 증식반응을 높게 유도하였으며, $CD4^+$ syngeneic T세포에서 IL-2와 $IFN-{\gamma}$의 생산량을 증가시키고, $CD8^+$ syngeneic T세포에서는 $IFN-{\gamma}$ 생산량을 증가시키는 것을 확인하였다. 이상의 결과로 crude saponin의 경우 수지상세포 의 세포표면 공동자극분자의 발현을 유도하고 성숙을 유도함으로써 T세포의 활성을 증진시키는 것으로 생각되며, 물 extract와 식용발효주정 extract는 crude saponin과는 다른 기작으로 T세포 활성화를 유도하는 것을 알 수 있었다. 따라서 실험에 사용한 홍삼시료, 즉 물 extract, 식용발효주정 extract, crude saponin 모두 수지상세포의 활성을 유도하는 물질로써 암항원 특이적 T세포 활성화를 이용한 항암치료에 이용할 수 있는 가능성이 있다고 사료된다.

Keywords

References

  1. Chang, Y. S., Chang, Y. H. and Sung, J. H. : The effect of ginseng and caffeine products on the antioxidative activities of mouse kidney. J. Ginseng Res. 30, 15-21 (2006) https://doi.org/10.5142/JGR.2006.30.1.015
  2. Park, M. G. : Korean ginseng. Korea Ginseng and Tobacoo Research institute, Seoul Korea, p.63 (1994)
  3. Brekhman, I. I. : Gosudarst lsdat et Med. Lit. Leningrad. 1-18 (1957)
  4. Kim, N. D., Han, B. H., Lee, E. B. and Kang, J. Y. : Studies of ginseng on antistress effects. Kor. J. Pharmacog. 10, 61-67 (1979)
  5. Joo, C. N. : The preventive effect on the saponin fraction of Panax ginseng C. A. Meyer against ethanol intoxication of rat liver. Proc. 4th Int'l. Ginseng Symp. 63-74 (1984)
  6. Elma, Z. T., Ilian, E. Z. and Christina, I. H. : Effect of ginsenoside $Rg_1$ on insulin binding in mice liver and brain membrane. Phytotheraphy Res. 5, 46-48 (1991) https://doi.org/10.1002/ptr.2650050114
  7. Henishin, C. C., Lee, R., Wang, L. C. and Liu, H. J. : Effect of ginsenoside $Rb_1$ on central cholinergic metabolism. Phamacology. 42, 223-229 (1991)
  8. Kang, S. Y., Kim, S. H., Schini, V. B. and Kim, N. D. : Dietary ginsenosides endothlium dependent relaxation in the thoracic arota of hydercholesterolemic rabbit. Gen. Pharmac. 26, 483-487 (1995) https://doi.org/10.1016/0306-3623(95)94002-X
  9. Fearon, D. T., and Locksley, R. M. : The instructive role of innate immunity in the acquired immune respones. Science. 272, 50-53 (1996) https://doi.org/10.1126/science.272.5258.50
  10. Brightbill, H. D., Libraty, D. H., Krutzik, S. R., Yang, R. B., Belisle, J. T., Bleharski, J. R., Maitland, M., Norgard, M. V., Plevy, S. E., Smale, S. T., Brennan, P. J., Bloom, B. R., Godowski, P. J. and Modlin, R. L. : Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 285, 732-736 (1999) https://doi.org/10.1126/science.285.5428.732
  11. Aliprantis, A. O., Yang, R. B., Mark, M. R., Suggett, S., Devaux, B., Radolf, J. D., Klimpel, G. R., Godowski, P. and zychlinsky, A. : Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science. 285, 736-739 (1999) https://doi.org/10.1126/science.285.5428.736
  12. Steinman, R. M. : The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271-296 (1991) https://doi.org/10.1146/annurev.iy.09.040191.001415
  13. Hart, D. N. : Dendritic cells : unique leukocyte populations which control the primary immune response. Blood. 90, 3245-3287 (1997)
  14. Bell, D., Young, J. W. and Banchereau, J. : Dendritic cells. Adv. Immunol. 72, 232-255 (1999) https://doi.org/10.1016/S0065-2776(08)60023-1
  15. Banchreau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y. J., Pulendran, B. and Plaucka, K. : Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767-811 (2000) https://doi.org/10.1146/annurev.immunol.18.1.767
  16. Kronin, V., Winkel, K., Suss, G., Kelso, A., Heath, W., Kirberg, J., Von Boehmer, H. and Shortman, K. : A subclass of dendritic cells regulates the response of naive CD8 T cells by limiting their IL-2 production. J. Immunol. 157, 3819-3827 (1996)
  17. Suss, G. and Shortman, K. : A subclass of dendritic cells kills CD4 Tcells via Fas/Fas-ligand-induced apoptosis. J. Exp. Med. 183, 1789-1796 (1996) https://doi.org/10.1084/jem.183.4.1789
  18. Baskar, S., Clemens, V., Glimcher, L., Nabavi, N. and Ostrand-Rosenberg, S. : Rejection of MHC class II-transduced tumor cells requires induction of tumor-encoded B7- 1 and/or B7-2 costimulatory molecules. J. Immunol. 156, 3821-3827 (1996)
  19. Fields, R. C., Shimizu, K. and Mule, J. J. : Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc. Natl. Acad. Sci. USA. 95, 9482-9487 (1998)
  20. Boczkowske, D., Nair, S.K., snyder, D. and Gilboa, E. : Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J. Exp. Med. 184, 465-472 (1996) https://doi.org/10.1084/jem.184.2.465
  21. Zitvogel, L., Mayordomo, J. I., Tjandrawan, T., DeLeo, A. B., Clarke, M. R., Lotze, M. T. and Storkus, W. J. : Therapy of murine tumors with tumor peptide-pulse dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J. Exp. Med. 183, 87-97 (1996) https://doi.org/10.1084/jem.183.1.87
  22. Fong, L. and Engleman, E. G. : Dendritic cells in cancer immunotherapy. Annu. Rev. Immunol. 18, 245-273 (2000) https://doi.org/10.1146/annurev.immunol.18.1.245
  23. Timmerman, J. M. and Levy, R. : Dendritic cell vaccines for cancer immunotherapy. Annu. Rev. Med. 50, 507-529 (1999) https://doi.org/10.1146/annurev.med.50.1.507
  24. Ahuja, S. S., Reddick, R. L., Sato, N., Montalbo, E., Kostecki, V., Zhao, W., Dolan, M. J., Melby, P. C. and Ahuja, S. K. : Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracelluar infection. J. Immunol. 163, 3890-3897 (1999)
  25. Zheng, L., Hung, X. L., Fan, Z., Borowski, L., Wilson, C. C. and Rinaldo, C. R. : Delivery of liposome-incapsulated HIV type 1 proteins to human dendritic cells for stimulation of HIV type1-specific memory cytotoxic T lymphocyte responses. AIDS Res. Hum. Retroviruses. 15, 1011-1020 (1999) https://doi.org/10.1089/088922299310520
  26. Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., Muramatsu, S. and Steinman. R. M. : Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 176, 1693-1702 (1992) https://doi.org/10.1084/jem.176.6.1693