Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Anti-Allergic Effects of Nodakenin in IgE/Ag-Induced Type I Hypersensitivity

노다케닌의 항 알러지 효과

  • Kim, Yong-Jae (Division of Biological Science and Technology, College of Science and Technology, Yonsei University) ;
  • Park, Sae-Jin (Division of Biological Science and Technology, College of Science and Technology, Yonsei University) ;
  • Kim, Tack-Joong (Division of Biological Science and Technology, College of Science and Technology, Yonsei University)
  • 김용재 (연세대학교 과학기술대학 생명과학기술학부) ;
  • 박세진 (연세대학교 과학기술대학 생명과학기술학부) ;
  • 김택중 (연세대학교 과학기술대학 생명과학기술학부)
  • Received : 2011.09.29
  • Accepted : 2011.12.06
  • Published : 2011.12.31
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Abstract

Mast cells are major effector cells associated with allergic responses. They are activated through the release of histamine, arachidonic acid, and proinflammatory cytokines. We investigated the effect of nodakenin, derived from the roots of Angelica gigas Nakai, on mast cell degranulation and on an allergic response in an animal model. We also investigated the effect of nodakenin on expression of multiple cytokines. Nodakenin suppressed the release of ${\beta}$-hexosaminidase, a marker of degranulation, as well as the expression of interleukin IL-4 and TNF-${\alpha}$ mRNA. Nodakenin inhibited the passive cutaneous anaphylaxis (PCA) reaction in ICR mice in a dose-dependent manner. These results suggest that nodakenin can inhibit mast cell degranulation through the inhibition of IL-4 and TNF-${\alpha}$ mRNA expression, and that nodakenin may potentially serve as an anti-allergic agent.

현재 전 세계적으로 알러지 질환은 급격히 증가하고 있는 추세이다. 기존의 길항제나 항원 특이적 면역 치료법의 부작용으로 인하여 항 알러지 작용에 효과적인 천연 기능성 물질에 대한 연구가 알러지 질환 치료의 유망한 분야로 여겨지고 있다. 비만세포는 히스타민이나 아라키돈 산, 그리고 전 염증성 사이토카인 등을 방출하는 알러지 반응에 주요하게 작용하는 효과세포이다. 우리는 참당귀의 뿌리로부터 추출한 노다케닌의 알러지 반응 억제효과에 대해서 연구하였다. 노다케닌을 이용하여 비만세포에서의 탈 과립현상 억제 효과를 측정한 결과, 비만세포에서 노다케닌이 탈과립의 표지인 ${\beta}$-hexosaminidase의 방출량을 농도 의존적으로 억제하는 것을 관찰하였고, 이러한 탈과립 억제 현상이 다양한 사이토카인 중 IL-4과 TNF-${\alpha}$의 양을 감소시킴으로써 매개된다는 사실을 RT-PCR을 통해 확인하였다. 또한 쥐에서 수동피부과민반응을 유도하여 노다케닌을 경구투여 했을 때 알러지성 과민반응 증상을 효과적으로 억제하는 것을 관찰하였다. 결과적으로, 이러한 결과들은 노다케닌이 항 알러지 약물의 개발에 잠재적인 후보물질이 될 수 있음을 시사한다.

Keywords

References

  1. Bansal, G., Z. Xie, S. Rao, K. Nocka, and K. Druey. 2008. Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat. Immunol. 9, 73-80. https://doi.org/10.1038/ni1533
  2. China Pharmacopoeia Committee. 1999. Pharmacopoeia of the People's Republic of China (The first division of 2000 edition). pp. 167, China Chemical Industry Press, Beijing.
  3. Frossi, B., J. Rivera, E. Hirsch, and C. Pucillo. 2007. Selective activation of Fyn/PI3K and p38 MAPK regulates IL-4 production in BMMC under nontoxic stress condition. J. Immunol. 178, 2549-2555. https://doi.org/10.4049/jimmunol.178.4.2549
  4. Granberg, M., C. Fowler, and S. Jacobsson. 2001. Effects of the cannabimimetic fatty acid derivatives 2-arachidonoylglycerol, anandamide, palmitoylethanolamide and methanandamide upon IgE-dependent antigen-induced beta- hexosaminidase, serotonin and TNF alpha release from rat RBL-2H3 basophilic leukaemic cells. Naunyn. Schmiedebergs Arch. Pharmacol. 364, 66-73. https://doi.org/10.1007/s002100100424
  5. Gregory, G. D. and M. Brown. 2006. Mast cells in allergy and autoimmunity: implications for adaptive immunity. Methods Mol. Biol. 315, 35-50.
  6. Han, E. H., J. H. Park, J. Y. Kim, Y. C. Chung, and H. G. Jeong. 2009. Inhibitory mechanism of saponins derived from roots of Platycodon grandiflorum on anaphylactic reaction and IgE-mediated allergic response in mast cells. Food Chem. Toxicol. 47, 1069-1075. https://doi.org/10.1016/j.fct.2009.01.041
  7. Itoh, T., K. Ohguchi, M. Iinuma, Y. Nozawa, and Y. Akao. 2008. Inhibitory effects of polymethoxy flavones isolated from Citrus reticulate on degranulation in rat basophilic leukemia RBL-2H3: enhanced inhibition by their combination. Bioorg. Med. Chem. 16, 7592-7598. https://doi.org/10.1016/j.bmc.2008.07.018
  8. Itoh, T., M. Oyama, N. Takimoto, C. Kato, Y. Nozawa, Y. Akao, and M. Iinuma. 2009. Inhibitory effects of sesquiterpene lactones isolated from Eupatorium chinense L. on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. Bioorg. Med. Chem. 17, 3189-3197. https://doi.org/10.1016/j.bmc.2009.02.062
  9. Lee, J. H., J. W. Kim, N. Y. Ko, S. H. Mun, E. Her, B. K. Kim, J. W. Han, H. Y. Lee, M. A. Beaven, Y. M. Kim, and W. S. Choi. 2008. Cucumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk. Clin. Immunol. 121, 1225-1231.
  10. Lee, J. H., J. W. Kim, N. Y. Ko, S. H. Mun, D. K. Kim, J. D. Kim, H. S. Won, H. S. Shin, H. S. Kim, E. Her, Y. M. Kim, and W. S. Choi. 2008. Mast cell-mediated allergic response is suppressed by Sophorae flos: inhibition of SRC-family kinase. Exp. Biol. Med. 233, 1271-1279. https://doi.org/10.3181/0803-RM-89
  11. Lee, J. H., J. W. Kim, N. Y. Ko, S. H. Mun, D. K. Kim, J. D. Kim, H. S. Won, H. S. Shin, H. S. Kim, Y. M. Kim, and W. S. Choi. 2008. Mast cell-mediated allergic response is suppressed by Sophorae flos: inhibition of SRC-family kinase. Exp. Biol. Med. 233, 1271-1279. https://doi.org/10.3181/0803-RM-89
  12. Lorentz, A., I. Klopp, T. Gebhardt, M. Manns, and S. Bischoff. 2003. Role of activator protein 1, nuclear factor- kappaB, and nuclear factor of activated T cells in IgE receptor-mediated cytokine expression in mature human mast cells. J. Allergy Clin. Immunol. 111, 1062-1068. https://doi.org/10.1067/mai.2003.1342
  13. Sakai, S., T. Sugawara, K. Matsubara, and T. Hirata. 2009. Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregatioin of high affinity IgE receptors. J. Biol. Chem. 284, 28172-28179. https://doi.org/10.1074/jbc.M109.001099
  14. Tiwari, N., C. Wang, C. Brochetta, G. Ke, F. Vita, Z. Qi, J. Rivera, M. Soranzo, G. Zabucchi, W. Hong, and U. Blank. 2008. VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways. Blood 111, 3665-3674. https://doi.org/10.1182/blood-2007-07-103309
  15. Wedemeyer, J., M. Tsai, and S. Galli. 2000. Roles of mast cells and basophils in innate and acquired immunity. Curr. Opin. Immunol. 12, 624-631. https://doi.org/10.1016/S0952-7915(00)00154-0

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