Dehydroepiandrosterone Sulfate Inhibited Immune Dysfunction Induced by LP-BM5 Leukemia Retrovirus Infection through Regulating Th1/Th2 Type Cytokine mRNA Expression and Oxidative Stress in Murine AIDS Model

LP-BM5 Leukemia Retrovirus 감염으로 유발된 Murine AIDS에서 Dehydroepiandrosterone Sulfate의 Th1/Th2 Cytokines의 발현 조절 및 산화적 스트레스 억제 효과 연구

  • 이정민 (남부대학교 식품영양학과)
  • Published : 2006.12.29


LP-BM5 murine leukemia retrovirus induces the excessive oxidative stress and immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dysfunction. In the present study, the immune restoratory effect of antioxidant hormone dedydroepiandrosterone sulfate (DHEAS) was investigated in the primary splenocytes from LP-BM5 retrovirus-infected C57BL/6 mice. DHEAS significantly increased T and B cell response to mitogen and normalized the unbalanced production of Th1/Th2 type cytokines. In particular, both protein and mRNA expression of IL-4, IL-6, and $TNF-\alpha$ were down-regulated by DHEAS treatment whereas IL-2 and $IFN-\gamma$ level were increased. This result suggests that DHEAS directly or indirectly regulates the gene expression of Th1/Th2 type cytokines in transcription level. In addition, DHEAS treatment decreased the hepatic lipid peroxidation and preserved vitamin E level in liver cells. These results suggested that DHEAS could effectively prevent immune dysfunction by regulating cytokine secretion and preventing the oxidative stress in murine AIDS.


  2. Lee J, Park CS, Chung MY, Cho DH, Watson RR. 2005. Reduced micronutrient intake accentuates premature death caused by immune dysfunction in leukemia retrovirus-infected C57BL/6 mice. Nutr Res 25: 401-412
  3. Lee YW, Hirani AA, Kyprianou N, Toborek M. 2005. Human immunodeficiency virus-1 Tat protein up-regulates IL-6 and IL-8 expression in human breast cancer cells. Inflamm Res 54: 380-389
  5. Gulow K, Kaminski M, Darvas K, Suss D, Li-Weber M, Krammer PH. 2005. HIV-1 tansactivator of transcription substitutes for oxidative signaling in activation-induced T cell death. J Immunol 174: 5249-5260
  6. Khorram O, Vu L, Yen SS. 1997. Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. J Gerontol A Biol Sci Med Sci 52: M1-7
  7. Sakakura Y, Nakagawa Y, Ohzeki T. 2006. Differential effect of DHEA on mitogen-induced proliferation of T and B lymphocytes. J Steroid Biochem Mol Biol 99: 115-120
  8. Aragno M, Tamagno E, Boccuzzi G, Brignardello E, Chiarpotto E, Pizzini A, Danni O. 1993. Dehydroepiandrosterone pretreatment protects rats against the pro-oxidant and necrogenic effects of carbon tetrachloride. Biochem Pharmacol 46: 1689-1694
  9. Liang B, Jiang S, Zhang G, Inserra P, Lee J, Solkoff D, Watson RR. 2001. Anti-inflammatory effects of theophylline: modulation of immune functions during murine leukemia virus infection. Immunopharmacol Immunotoxicol 23: 307-317
  11. Burton GW, Webb A, Ingold KU. 1985. A mild, rapid, and efficient method of lipid extraction for use in determining vitamin E/lipid ratios. Lipids 20: 29-39
  12. Jiang S, Lee J, Zhang Z, Inserra P, Solkoff D, Watson RR. 1998. DHEA synergizes with antioxidant supplements for immune restoration in old as well as retrovirus-infected mice. J Nutr Biochem 9: 362-369
  13. Parasad AS. 2000. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 182: s62-s68
  14. Kanagawa O, Vaupel BA, Gayma S, Koehler G, Kopf M. 1993. Resistance of mice deficient in IL-4 to retrovirus- induced immunodeficiency syndrome (MAIDS). Science 262: 240-242
  15. Wang Y, Ardestani SK, Liang B, Bechham C, Watson RR. 1994. Anti-IL-4 monoclonal antibody and interferon-gamma administration retards development of immune dysfunction and cytokine dysregulation during murine AIDS. Immunol 83: 384-389
  16. Solerte SB, Ferrari E, Cuzzoni G, Locatelli E, Giustina A, Zamboni M, Schifino N, Rondanelli M, Gazzaruso C, Fioravanti M. 2005. Decreased release of the angiogenic peptide vascular endothelial growth factor in Alzheimer's disease: recovering effect with insulin and DHEA sulfate. Dement Geriatr Cogn Disord 19: 1-10
  17. Sappinton RM, Calkins DJ. 2006. Pressure-induced regulation of IL-6 in retinal glial cells: involvement of the ubiquitin/proteasome pathway and NF-$_KB$. Invest Ophthalmol Vis Sci 47: 3860-3869
  18. Dillon JS. 2005. DHEA, DHEAS and related steroids: their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy 4: 377-385
  19. Victoriano AF, Asamitsu K, Hibi Y, Imai K, Barzaga NG, Okamoto T. 2006. Inhibition of HIV-1 replication in latently infected cells by a novel I-$\kappa$B kinase inhibitor. Antimicrob Agents Chemother 50: 547-555

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