Pycnogenol, a Standardized Extract of French Maritime Pine Bark, Inhibited the Transcriptional Expression of Th2 Cytokines by Suppressing $NF-{\kappa}B$ Activation in Primary Splenocytes of C57BL/6 Mice with Murine AIDS

Murine AIDS 감염쥐 splenocytes에서 $NF-{\kappa}B$의 활성화 억제를 통한 pycnogenol의 Th2 cytokines의 mRNA 발현 조절 효과

  • 이정민 (남부대학교 식품영양학과)
  • Published : 2006.12.31

Abstract

LP-BM5 murine leukemia retrovirus induces the immune dysfunction by imbalanced secretion of Th1 and Th2 cytokines in the murine AIDS model. In the present study, it was investigated whether pycnogenol (Pyc) administration could deactivate $NF-{\kappa}B$ to regulate the gene expression of Th1 and Th2 cytokines in C57BL/6 mice with murine AIDS. Treatment with Pyc for 12 weeks significantly inhibited the loss of body weight and enlargement of spleen and lymph node usually seen with AIDS. Moreover, Pyc increased the plasma level of Th1 cytokines, IL-2 and $IFN-{\gamma}$, while reducing the plasma level of Th2 cytokines, IL-6, IL-10, and $TNF-{\alpha}$. In primary culture of splenocytes, mRNA expression of Th2 cytokines was suppressed, but that of Th1 cytokines was not affected. The LP-BM5 retrovirus infection stimulated the cytoplasmic activation of $NF-{\kappa}B$ and nuclear translocation of $I-{\kappa}B$, whereas Pyc administration significantly reduced $NF-{\kappa}B$ activation and $I-{\kappa}B$ degradation. These results suggested that the inhibitory effect of Pyc on Th2 cytokines in mice with murine AIDS was dependent on suppression of the $NF-{\kappa}B$ signaling pathway and was not dependent on $INF-{\gamma}$ level, which regulates Th2 cytokines.

Keywords

pycnogenol;murine AIDS;splenocytes;Th2 cytokines;$NF-{\kappa}B$

References

  1. Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 74: 855-862 (2004) https://doi.org/10.1016/j.lfs.2003.07.037
  2. Grimm T, Schafer A, Hogger PF. Antioxidant activity and inhibition of matrix metallo-proteinase by metabolites of maritime pine bark extract. Free Radic. BioI. Med. 36: 811-822 (2004) https://doi.org/10.1016/j.freeradbiomed.2003.12.017
  3. Veurink G, Liu D, Taddei K, Perry Gm Smith MA, Robertson TA, Hone E, Groth DM, Atwood CS, Martins RN. Reduction of inclusion body in ApoE-deficient mice fed a combination of antioxidants. Free Radic. Biol. Med. 34: 1070-1077 (2003) https://doi.org/10.1016/S0891-5849(03)00042-X
  4. Wang Y, Ardestani SK, Liang B, Bechham C, Watson RR. Anti-IL- 4 monoclonal antibody and interferon-gamma administration retards development of immune dysfunction and cytokine dysregulation during murine AIDS. Immunol. 83: 384-389 (1994)
  5. Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of $NF-{\kappa}B$ activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid. Redox Signal 7: 395-403 (2005) https://doi.org/10.1089/ars.2005.7.395
  6. Victoriano AF, Asamitsu K, Hibi Y, Imai K, Barzaga NG, Okamoto T. Inhibition of HIV-1 replication in latently infected cells by a novel $I-{\kappa}B$ kinase inhibitor. Antimicrob. Agents Chemother. 50: 547-555(2006) https://doi.org/10.1128/AAC.50.2.547-555.2006
  7. Maritim A, Dene BA, Sanders RA, Watkins JB. Effect of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats. J. Biochem. Mol. Toxicol. 17: 193-199 (2003) https://doi.org/10.1002/jbt.10078
  8. Lee J, Kim N, Cho DH, Chung MY, Hwang KT, Kim HJ, Jun W, Park CS. Ethanol extract of Oenanthe javanica modulates inflammatory response by inhibiting $NF-{\kappa}B$ mediated COX-2 expression in RAW 264.7 macrophage. Food Sci. Biotechnol. 15: 303-307 (2006)
  9. Kanagawa O,Vaupel BA, Gayma S, Koehler G,Kopf M. Resistance of mice deficient in IL-4 to retrovirus-induced immunodeficiency syndrome (MAIDS). Science 62: 240-242 (1993) https://doi.org/10.1126/science.62.1602.240
  10. Meanwell NA, Kadow JF. Inhibitors of the entry of HIV into host cells. Curr. Opin. Drug Discov. Devel. 6: 451-461 (2003)
  11. Lee YW, Hirani AA, Kyprianou N, Toborek M. Human immunodeficiency virus-1 Tat protein up-regulates IL-6 and IL-8 expression in human breast cancer cells. lnflamm. Res. 54: 380-389 (2005) https://doi.org/10.1007/s00011-005-1371-8
  12. Crinelli R, Bianchi M, Gentilini L, Magnani M, Hiscott J. Activation of the ubiquitin proteolytic system in murine acquired immunodeficiency syndrome affects I-kappa B alpha turnover. Eur.J. Biochem. 263: 202-211 (1999) https://doi.org/10.1046/j.1432-1327.1999.00485.x
  13. Parasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J. Infect. Dis. 182: s62-s68 (2000) https://doi.org/10.1086/315916
  14. Huang WC, Chen JJ, Chen CC. c-Src-dependent tyrosine phosphorylation of IKKbeta is involved in tumor necrosis factor-alpha- induced intercellular adhesion molecule-1 expression. J. Biol. Chem. 278: 9944-9952 (2003) https://doi.org/10.1074/jbc.M208521200
  15. Lee J, Jiang S, Liang B, Inserra P, Zhen Z, Solkoff D, Watson RR. Antioxidant supplementation in prevention and treatment of immune dysfunction and oxidation induced by murine AIDS in old mice. Nutr. Res. 18: 327-339 (1998) https://doi.org/10.1016/S0271-5317(98)00025-6
  16. Devaraj S, Vega-Lopez S, Kaul N, Schonlau F, Rohdewald P, Jialal I. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids 37: 931-934 (2002) https://doi.org/10.1007/s11745-006-0982-3
  17. Lee J, Hwang KT, Lee JM, Kim SH, Watson RR, Park KY. Supplementation of French maritime pine bark extract prevents lung injury and lipid peroxidation in nude mice exposed to side-stream cigarette smoke. J. Food Sci. Nutr. 9: 65-70 (2003)
  18. Saeed H, Lee J, Watson RR. Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic. Biol. Med. 30: 154-169 (2001) https://doi.org/10.1016/S0891-5849(00)00445-7
  19. Gasparis AP, Tassiopoulos AK. Nutritional support in the patient with HIV infection. Nutrition 17: 981-982 (2001) https://doi.org/10.1016/S0899-9007(01)00707-9
  20. Lee J, Park CS, Chung MY, Cho DH, Watson RR. Reduced micronutrient intake accentuates premature death caused by immune dysfunction in leukemia retrovirus-infected C57BL/6 mice. Nutr. Res. 25: 401-412 (2005) https://doi.org/10.1016/j.nutres.2004.12.010
  21. Liang B, Jiang S, Zhang G, Inserra P, Lee J, Solkoff D, Watson RR. Anti-inflammatory effects of theophylline: modulation of immune functions during murine leukemia virus infection. Immunopharmacol. Immunotoxicol. 23: 307-317 (2001) https://doi.org/10.1081/IPH-100107332
  22. Gulow K, Kaminski M, Darvas K, Suss D, Li-Weber M, Krammer PH. HIV-1 tansactivator of transcription substitutes for oxidative signaling in activation-induced T cell death. J. Immunol. 174: 5249-5260 (2005) https://doi.org/10.4049/jimmunol.174.9.5249