DOI QR코드

DOI QR Code

Lipopolysaccharide에 의한 RAW264.7 세포의 염증매개물질 생성에 대한 Septicine의 저해 활성

Septicine Inhibits the Production of Inflammatory Mediators in Lipopolysaccharide-Stimulated Murine Macrophages

  • 박근묵 (대구가톨릭대학교 의생명과학과) ;
  • 김진경 (대구가톨릭대학교 의생명과학과)
  • Park, Geun-Mook (Department of Biomedical Science, College of Natural Science, Catholic University of Daegu) ;
  • Kim, Jin-Kyung (Department of Biomedical Science, College of Natural Science, Catholic University of Daegu)
  • 투고 : 2011.07.25
  • 심사 : 2011.08.30
  • 발행 : 2011.09.30

초록

염증은 바이러스 등의 병원체 및 다양한 물리.화학적 스트레스에 의하여 일어나는 생체방어 반응이나, 과도한 염증반응은 세포독성과 다양한 질환을 일으킨다. 따라서 염증반응에서 생성되는 과도한 염증매개물질들을 억제함으로 다양한 염증질환을 예방, 치료 할 수 있다. 본 연구에서는 Tylophora asthmatica, Tylophora ovata 등에 함유되어 있는 생리활성 성분인 septicine의 항염증 효과를 연구하였다. 생쥐의 대식세포주인 RAW264.7 세포에 lipopolysaccharide (LPS)를 처리하여 염증반응을 유도하고, septicine를 처리한 결과, septicine은 LPS 처리에 의한 nitric oxide (NO) 및 염증성 사이토카인의 분비를 현저히 억제시키는 것을 관찰 할 수 있었으며, NO의 생합성효소인 iNOS 단백질의 발현 또한 억제시킴을 확인 할 수 있었다. 이러한 연구결과는 염증반응을 조절하는 후보물질로써의 septicine의 가능성을 보여주는 것이다.

Anti-inflammatory activities of septicine, a natural alkaloid product present in the leaves and stems of Tylophora ovata, were evaluated in lipopolysaccharide (LPS)-stimulated murine macrophages, RAW264.7 cells. Treatment with septicine inhibited LPS-induced nitric oxide (NO), inflammatory cytokines, tumor necrosis factor-${\alpha}$ and interleukin-6 production in a concentration-dependant manner. In addition, septicine suppressed the expression of inducible NO synthase. These results suggest that the anti-inflammatory activities of septicine might be attributed to the inhibition of NO, iNOS and cytokine expression.

키워드

참고문헌

  1. Chen, G. Y. and G. Nunez. 2010. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10, 826-837. https://doi.org/10.1038/nri2873
  2. Comins, D. L., X. Chen, and L. A. Morgan. 1997. Enantiopure N-acyldihydropyridones as synthetic intermediates: asymmetric synthesis of (-)-septicine and (-)-tylophorine. J. Org. Chem. 62, 7435-7438. https://doi.org/10.1021/jo9711495
  3. Fujiwara, N. and K. Kobayashi. 2005. Macrophages in inflammation. Curr. Drug Targets Inflamm. Allergy 4, 281-286. https://doi.org/10.2174/1568010054022024
  4. Gehr, G., T. Braun, and W. Lesslauer. 1992. Cytokines, receptors, and inhibitors. Clin. Investig. 70, 64-69. https://doi.org/10.1007/BF00422944
  5. Haustedt, L. O., C. Mang, K. Siems, and H. Schiewe. 2006. Rational approaches to natural-product-based drug design. Curr. Opin. Drug Discov. Devel. 9, 445-462.
  6. Kohl, J. 2006. Self, non-self, and danger: a complementary view. Adv. Exp. Med. Biol. 586, 71-94. https://doi.org/10.1007/0-387-34134-X_6
  7. Lee, B. G., S. H. Kim, O. P. Zee, K. R. Lee, H. Y. Lee, J. W. Han, and H. W. Lee. 2000. Suppression of inducible nitric oxide synthase expression in RAW 264.7 macrophages by two-carboline alkaloids extracted from Melia azedarach. Eur. J. Pharmacol. 406, 301-309. https://doi.org/10.1016/S0014-2999(00)00680-4
  8. Lee, Y. Z., C. W. Huang, C. W. Yang, H. Y. Hsu, I. J. Kang, Y. S. Chao, I. S. Chen, H. Y. Chang, and S. J. Lee. 2011. Isolation and biological activities of phenanthroindolizidine and septicine alkaloids from the formosan Tylophora ovata. Planta. Med. DOI: 10.1055/s-0030-1271199.
  9. MacEwan, D. J. 2002. TNF receptor subtype signalling: differences and cellular consequences. Cell Signal. 14, 477-492. https://doi.org/10.1016/S0898-6568(01)00262-5
  10. Michael, J. P. 2001. Indolizidine and quinolizidine alkaloids. Nat. Prod. Rep. 18, 520-542. https://doi.org/10.1039/b005384h
  11. Scheller, J., A. Chalaris, D. Schmidt-Arras, and S. Rose-John. 2011. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta. 1813, 878-888. https://doi.org/10.1016/j.bbamcr.2011.01.034
  12. Tsan, M. F. and B. Gao. 2007. Pathogen-associated molecular pattern contamination as putative endogenous ligands of Toll-like receptors. J. Endotoxin Res. 13, 6-14. https://doi.org/10.1177/0968051907078604
  13. Valledor, A. F., M. Comalada, L. F. Santamaria-Babi, J. Lloberas, and A. Celada. 2010. Macrophage proinflammatory activation and deactivation: a question of balance. Adv. Immunol. 108, 1-20. https://doi.org/10.1016/B978-0-12-380995-7.00001-X
  14. Zhang, X. and D. M. Mosser. 2008. Macrophage activation by endogenous danger signals. J. Pathol. 214, 161-178. https://doi.org/10.1002/path.2284
  15. Zhou, G., M. C. Gingras, S. H.Liu, D. Li, Z. Li, R. L. Catania, K. M. Stehling, M. Li, G. Paganelli, R. A. Gibbs, F. J. Demayo, W. E. Fisher, F. C. Brunicardi. 2011. The hypofunctional effect of P335L single nucleotide polymorphism on SSTR5 function. World J. Surg. 35, 715-724.