Archives of Pharmacal Research

  • 제25권3호
  • /
  • Pages.364-369
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  • 2002
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Identification of Hepatitis C Virus Core Domain Inducing Suppression of Allostimulatory Capacity of Dendritic Cells

  • Kim, Ho-Sang (Department of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Lee, Jae-Kwon (Department of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Yang, In-Ho (Department of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Ahn, Jeong-Keun (Department of Microbiology, Chungnam National University) ;
  • Oh, Yoon-I (Department of Veterinary Medicine, Chungnam National University) ;
  • Kim, Chul-Joong (Department of Veterinary Medicine, Chungnam National University) ;
  • Kim, Young-Sang (Department of Biochemistry, Chungnam National University) ;
  • Lee, Chong-Kil (College of Pharmacy, Chung-buk National University)
  • 발행 : 2002.06.01
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초록

Hepatitis C virus (HCV) is remarkably efficient at establishing chronic infection. One of the reasons for this appears to be the suppression of the accessory cell function of professional antigen presenting cells. In the present study, the immunosuppressive activity of HCV protein was examined on dendritic cells (DCs) generated from mouse bone marrow progenitor cells in vitro. We found that the DCs forced to express HCV protein have defective allostimulatory ability. DCs expressing HCV protein were phenotypically indistinguishable from normal DCs. However, they were unable to produce IL-12 effectively when stimulated with lipopolysaccharide. The functional domain of the HCV protein essential for immunosuppression was determined using a series of ${NH_2}-and$ C-terminal deletion mutants of HCV core protein. We found that amino acid residues residing between the 21 st and the 40th residues from the ${NH_2}-terminus$ of HCV core protein are required for immunosuppression. These findings suggest that HCV core protein suppresses the elicitation of protective Th1 responses by the inhibition of IL-12 production by DCs.

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참고문헌

  1. Aiba, S., Tagami, H., Dendritic cell activation induced by various stimuli, e.g., exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellular matrix. J. Dermatol. Sci., 20, 1-13(1998) https://doi.org/10.1016/S0923-1811(99)00005-5
  2. Austyn, J. New insight into the mobilization and phagocytic activity of dendritic cells. J. Exp. Med., 183, 1287-1292(1996) https://doi.org/10.1084/jem.183.4.1287
  3. Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y. J., Pulendran, B., Palucka, K., Immunobiology of dendritic cells. Annu. Rev. Immunol., 18,767-811 (2000) https://doi.org/10.1146/annurev.immunol.18.1.767
  4. Cohen, J., The scientific challenge of hepatitis C. Science, 285, 26-30 (1999) https://doi.org/10.1126/science.285.5424.26
  5. Diepolder, H. M., Zachoval, R, Hoffmann, R. M., Wierenga, E. A., Santantonio, T., Jung, M. C., Eichenlaub, D., and Pape, G. R., Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet, 346,1006-1007 (1995) https://doi.org/10.1016/S0140-6736(95)91691-1
  6. Granucci, F., Ferrero, E., Foti, M., Aggujaro, D., Vettoretto, K., Ricciardi-Castagnoli, P., Early events in dendritic cell maturation induced by LPS. Microbes & Infection, 1, 1079-1084(1999) https://doi.org/10.1016/S1286-4579(99)00209-9
  7. Hiasa Y., Horiike, N., Akbar, F., Saito, I., Miyamura, T., Matsuura, Y., and Onji, M., Low stimulatory capacity of lymphoid dendritic cells expressing hepatitis C virus genes. Biochem. Biophys. Res. Commun., 249, 90-95 (1998) https://doi.org/10.1006/bbrc.1998.9089
  8. Kanto, T, Hayashi, N., Takehara, T., Tatsumi, T., Kuzushita, N., Ito, A., Sasaki, Y., Kasahara A., and Hori, M., impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. J. Immunol., 162,5584-5591 (1999)
  9. Lanzavecchia, A., Understanding the mechanisms of sustained signaling and T cell activation. J. Exp. Med. 185, 1717-1719(1997) https://doi.org/10.1084/jem.185.10.1717
  10. Large, M. K., Kittlesen, D. J., and Hahn, Y S., Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatitis C virus persistence. J Immunol., 162,931-938 (1999)
  11. Lechmann, M., Ihlenfeldt, H. G., Braunschweiger, I., Giers, G., Jung, G., Matz, B., Kaiser, R., Sauerbruch, T, and Spengler, U, T- and B-cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti-hepatitis C virus-positive blood donors without viremia. Hepatology, 24, 790-795 (1996)
  12. Lee C. H., Choi, Y. H., Yang, S.-H., Lee, G. W., Ha, S. J., and Sung, Y C., Hepatitis C virus care protein inhibits interleukin 12 and nitric oxide production from activated macrophages. Vrology, 279, 271-279 (2001) https://doi.org/10.1006/viro.2000.0694
  13. Lee J. K., Lee, M. K., Yun, Y-P., Kim, Y, Kim, J. S., Kim, Y S., Kim, K., Han, S. S. and Lee, C.-K., Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int. Immunopharmacol., 1, 1275-1284(2001) https://doi.org/10.1016/S1567-5769(01)00052-2
  14. Lerat, H., Berby, F., Trabaud, M. A., Vidalin, O., Major, M., Trepo, C., Inchauspe, G., Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells. J . Clin. Invest. 97, 845-51 (1996) https://doi.org/10.1172/JCI118485
  15. Manome, H., Aiba, S., Tagami, H. Simple chemicals can induce maturation and apoptosis of dendritic cells. Immunology, 98, 481-490 (1999) https://doi.org/10.1046/j.1365-2567.1999.00916.x
  16. Marusawa, H., Hijikata, M., Chiba, T., Shimotohno, K., Hepatitis C virus core protein inhibits Fas- and Tumor necrosis factor alpha-mediated apoptosis via NF-kB activation. J. Virol., 73, 4713-4720 (1999)
  17. Moldvay, J., Deny, P., Pol, S., Brechot C., Lamas, E., Detection of hepatitis C virus RNA in peripheral blood mononuclear cells of infected patients by in situ hybridization. Blood, 83, 269-73 (1994)
  18. Odeberg, J., Yun, Z., Sonnerborg, A., Bjora, K., Uhlen, M., and Lundeberg, J., Variations of hepatitis C virus hypervariable region 1 in immunocompromised patients. J. Infect. Dis., 175, 938-943 (1997) https://doi.org/10.1086/513995
  19. Purcell, R., The hepatitis C virus: overview. Hepatology, 26 (3suppl 1), 11S-14S (1997) https://doi.org/10.1002/hep.510260702
  20. Sung, Y. C., Mechanism of HCV chronic infections; core as a potential antiviral target. In The 48th Annual Convention of the Pharmaceutical Society of Korea and International Symphosium. The Pharmaceutical Society of Korea. pp139-140(1999)
  21. Tsai, S. L., Liaw, Y. F., Chen, M. H., Huang, C. Y, and Kuo, G. C., Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C chronicity. Hepatology, 25, 449-458 (1997) https://doi.org/10.1002/hep.510250233