$18{\beta}$-Glycyrrhetinic Acid Induces Protective Anti-Candida albicans Antibody by Its Immunoadjuvant Activity

$18{\beta}$-Glycyrrhetinic Acid의 면역보조제효능에 의한 항 전신성캔디다증 효과

  • Han, Yong-Moon (Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University)
  • 한용문 (동덕여자대학교 약학대학 면역.미생물학교실)
  • Published : 2008.12.31

Abstract

The role of antibody in the fungal infections is controversial. However, our previous reports showed a certain epitope in Candida albicans cell wall (CACW) induces protective antibody. A major problem is that the epitope isolation requires tremendous time with high cost. This aspect led us to investigate a simple way inducing protective antibodies against C. albicans. In the present study, we determined if $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) from Glabrae Radix (a family of Leguminosae) has immunoadjuvant activity. Data displayed that the $18{\beta}$-GA suppressed proliferations of both T- and Blymphocytes at high concentrations, whereas below 20 ${\mu}M$ concentration the compound supported the proliferations. These observations indicate that $18{\beta}$-GA has immunoregulatory activity. Based on this observation, an immunoadjuvant effect was examined at the low concentration. Results from animal experiments showed that CACW combined with or without $18{\beta}$-GA produced the anti-C. albicans antiserum in mice. Nevertheless, the CACW combined with $18{\beta}$-GA formula only protected mice against disseminated candidiasis (P<0.05). These data implicate that $18{\beta}$-GA has immunoadjuvant activity, which may provoke the CACW antigen to induce protective antibody. Currently, we are investigating possible mechanism of how the $18{\beta}$-GA provokes such protective immunity against the disseminated disease.

Keywords

References

  1. Han, Y. and Cutler, J. E. : Antibody response that protects against disseminated candidiasis. Infect. Immun. 63, 2714 (1995)
  2. Han, Y., Riesselman, M. H. and Cutler, J. E. : Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody. Infect. Immun. 68, 1649 (2000) https://doi.org/10.1128/IAI.68.3.1649-1654.2000
  3. Han, Y., Kozel, T. R., Zhang, M. X., MacGill, R. S., Carroll, M. C. and Cutler, J. E. : Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis. J. Immunol. 167, 1550 (2001) https://doi.org/10.4049/jimmunol.167.3.1550
  4. Banerjee, U., Mohapatra, L. N. and Kumar, R. : Role of antibody in defence against murine candidosis. Indian J. Med. Res. 79, 760 (1984)
  5. Lee, J. H. and Han, Y. : Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4+ T cell. Int. Immunopharm. 6, 1424 (2006) https://doi.org/10.1016/j.intimp.2006.04.009
  6. Lee, J. H., Lee, J. Y., Park, J. H., Jung, H. S., Kim, J. S., Kang, S. S., Kim, Y. S. and Han, Y. : Immunoregulatory activity by daucosterol, a beta-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine. 25, 3834 (2007) https://doi.org/10.1016/j.vaccine.2007.01.108
  7. Lee, J. H., Park, J. H., Kim, Y. S. and Han, Y. : Chlorogenic acid, a polyphenolic compound, treats mice with septic arthritis caused by Candida albicans. Int. Immunopharmacol. 8, 1681 (2008) https://doi.org/10.1016/j.intimp.2008.08.002
  8. Han, Y. : Effect of $18{\beta}$-glycyrrhetinic acid on septic arthritis caused by Candida albicans. Yakhak Hoeji. 51, 325 (2007)
  9. Inoue, H. and Mori, T. : Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema. B. J. Pharmacol. 96, 204 (1989) https://doi.org/10.1111/j.1476-5381.1989.tb11801.x
  10. Yano, S. and Harada, M. : Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models. Chem Pharm Bull. 37, 2500 (1989) https://doi.org/10.1248/cpb.37.2500
  11. Teelucksingh, S., Mackie, A. D., Burt, D., McIntyre, M. A., Brett, L. and Edwards, C. R. : Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet. 1060 (1990)
  12. Marandici, A. and Monder, C. : Inhibition by glycyrrhetinic acid of rat tissue 11-hydroxysteroid dehydrogenase in vivo. Steroids. 58, 153 (1993) https://doi.org/10.1016/0039-128X(93)90062-R
  13. Gumpricht, E., Dahl, R., Devereaux, M. W. and Sokol, R. J. : Licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. J. Biol. Chem. 280, 10556 (2005) https://doi.org/10.1074/jbc.M411673200
  14. MacLeod, M. K., McKee, A., Crawford, F., White, J., Kappler. J. and Marrack, P. : CD4 memory T cells divide poorly in response to antigen because of their cytokine profile. Proc. Natl. Acad. Sci. (USA) 23, 14521 (2008)
  15. Chen, G. H., McNamara, D. A., Hernandez, Y., Huffnagle, G. B., Toews, G. B. and Olszewski, M. A. : Inheritance of immune polarization patterns is linked to resistance versus susceptibility to Cryptococcus neoformans in a mouse model. Infect. Immun. 76, 2379 (2008) https://doi.org/10.1128/IAI.01143-07
  16. Weaver, C. T., Hatton, R. D., Mangan, P. R. and Harrington, L. E. : IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 25, 821 (2007) https://doi.org/10.1146/annurev.immunol.25.022106.141557
  17. Corthay, A. : A three-cell model for activation of naïve T helper cells. Scand. J. Immunol. 64, 93 (2006) https://doi.org/10.1111/j.1365-3083.2006.01782.x
  18. Kensil, C. R., Patel, U., Lennick, M. and Marciani, D. : Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. J. Immunol. 146, 431 (1991)
  19. Ghochikyan, A., Mkrtichyan, M., Loukinov, D., Mamikonyan, G., Pack, S. D., Movsesyan, N., Ichim, T. E., Cribbs, D. H., Lobanenkov, V. V. and Agadjanyan, M. G. : Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer-testis antigen, brother of the regulator of imprinted sites. J. Immunol. 178, 566 (2007) https://doi.org/10.4049/jimmunol.178.1.566
  20. White, K., Rades, T., Kearns, P., Toth, I. and Hook, S. : Immunogenicity of liposomes containing lipid core peptides and the adjuvant Quil A. Pharm Res. 23, 1473 (2006) https://doi.org/10.1007/s11095-006-0272-z
  21. Han, Y., Morrison, R. P. and Cutler, J. E. : A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection. Infect. Immun. 66, 5771 (1998)
  22. Han, Y., Kanbe, T. K., Cherniak, R. and Cutler, J. E. : Biochemical characterization of Candida albicans epitopes that can elicit protective and nonprotective antibodies. Infect. Immun. 65, 4100 (1997)
  23. Coutinho, A., Forni, L., Melchers, F. and Watanabe, T. : Genetic defect in responsiveness to the B cell mitogen lipopolysaccharide. Eur. J. Immunol. 7, 325 (1977) https://doi.org/10.1002/eji.1830070517
  24. Han, Y., van Rooijen, N. and Cutler, J. E. : Binding of Candida albicans yeast cells to mouse politeal lymph node is mediated by macrophages. Infect. Immun. 61, 3244 (1993)
  25. Han, Y., Ulrich, M. A. and Cutler, J. E. : Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis. J. Infect. Dis. 179, 1477 (1999) https://doi.org/10.1086/314779
  26. Han, Y., Jin B. S., Ko, S. K. and Lee, J. H. : Immunoactivity of ginsenosides Re and Rg1 that enhances resistance of mice against disseminated candidiasis. Nat. Prod. Sci. 10, 134 (2004)