Induction of Nitric Oxide and Cytokines in Macrophages by Codonopsis lanceolata

대식세포에서 산더덕에 의한 NO 생성 및 싸이토카인 유도효과

  • So, Mi-Sun (Microbia Corp. Limited Technical Research Institute) ;
  • Lee, Jin-Sil (Foodservice Management Nutrition, Sangmyung University) ;
  • Yi, Seh-Yoon (Department of Chemistry, Suwon University)
  • 소미선 ((주)마이크로비아 기술연구소) ;
  • 이진실 (상명대학교 외식영양학과) ;
  • 이세윤 (수원대학교 화학과)
  • Published : 2004.12.31

Abstract

The immunomodulatory effect of Codonopsis lanceolata based on the production of cytokines and the activation of macrophage was studied. The mRNA expression of nitric oxide synthase (iNOS) was gradually induced after 24 hr treatment of Codonopsis lanceolata, and NO production was a maximum after 24 hr treatment with 1 mg/mL. RAW 264.7 cell on in vitro treatment with Codonopsis lanceolata induced mRNA of cytokines such as interleukin-1(IL-1)${\beta}$, interleukin-6(IL-6), tumor necrosis $factor(TNF)-{\alpha}\;and\;interferon(IFN)-{\gamma}$; $IL-1{\beta}$ and IL-6 mRNA were gradually induced up to 24 hr, $TNF-{\alpha}\;mRNA$ was regularly induced up to 24 hr, and $IFN-{\gamma}\;mRNA$ level was a maximum within 1 hr. These results suggest that Codonopsis lanceolata exerts as an effective immunomodulator and enhances antitumor activity of macrophages.

대식세포는 IL-1, IL-6, $TNF-{\alpha},\;IFN-{\gamma}$의 중요한 근원이고, 전염성의 병원체와 종양 세포에 대해 저항하는 주요한 effector 세포이다. 이것은 cytokine signal에 의해 세포파괴가 되도록 활성화 된다. 이번 연구에서 우리는 산더덕의 물 추출물이 cytokine, nitric oxide와 같은 effector 분자를 유도하기 위해 대식세포를 활성화하는지를 알아보기 위하여 실험하였다. 산더덕 추출물에 의한 대식세포의 NO 생성은 농도 의존적이고, 시간 의존적이었다. iNOS는 시간이 지날수록 발현이 유도되었다. 산더덕 추출물에 의한 IL-1과 IL-6 mRNA 유도는 시간 의존적으로 증가 되었고, 처리 후 24시간에 최고점에 도달하였다. 이것은 활성화된 대식세포가 종양세포를 죽일 수 있음을 말한다. $TNF-{\alpha}\;mRNA$의 양은 시간이 지나도 일정하였고, $IFN-{\gamma}\;mRNA$의 양은 산더덕 추출물의 처리 1시간 후에 빠르게 강화되었다. 이러한 결과로부터 산더덕은 효과적인 면역조절자이고 대식세포의 항종양활성을 강화함을 알 수 있다.

Keywords

References

  1. Kim JH, Chung MH. Pharmacognostical studies on Codonopsis lanceolata. Korean J. Pharmacog. 6: 43-47 (1975)
  2. Chung MS. Composition and color of Codonopsis lanceolata affected by cultivation methods. Korean J. Diet. Cult. 14: 529-534 (1999)
  3. Yang HS, Choi SS, Han BH, Kang SS, Woo WS. Sterols and tripenoids from Codonopsis lanceolata. J. Pharm. Soc. Korea 19: 209-215 (1975)
  4. Chung BS, Im DS. On the composition from Codonopsis lanceolata (Benth. et Hook). Program the 25th annual convention of the pharmaceutical Society of Korea (1976)
  5. Chang YK, Kim SY, Han BH. Chemical studies on the alkaloidal constituents of Codonopsis lanceolata. Yakhakhoeji 30: 1 (1986)
  6. Park JY, Kim YH, Kim KS, Kwag JJ. Volatile flavor components of Codonopsis lanceolata Traut. (Benth. et Hook). J. Korean Agric. Chem. Soc. 32: 338-343 (1989)
  7. Kim JH, Kim KR, Kim JJ, Oh CH. Comparative sampling procedures for the volatile flavor components of Codonopsis lanceolata. Korean J. Food Sci. Technol. 24: 171-176 (1992)
  8. Maeng YS, Park HK. Antioxidant activity of ethanol extract from Dodok (Codonopsis lanceolata). Korean J. Food Sci. Technol. 23: 311-316 (1991)
  9. Han EG, Sung IS, Moon HG, Cho SY. Effects of Codonopsis lanceolata water extract on the level of lipid in rats fed high fat diet. J. Korean Soc. Food Sci. Nutr. 27: 940-944 (1998)
  10. Lee YJ, Kim JM, Jung YM. Effect of Codonopsis pilosuls on the cellular immunity. Korean J. Vet. Publ. Hlth. 19 (1995)
  11. Lee JH. Immunostimulative effect of hot-water extract from Codonopsis lanceolata on lymphocyte and clonal macrophage. Korean J. Food Sci. Technol. 34: 732-736 (2002)
  12. Suh JS. Effect of Codonopsis lanceolata Radix water extract on immunocytes. Korean J. Food Nutr. 9: 379-384 (1996)
  13. Suh JS, Eun JS. Isolation of active components on immunocytes from Codonopsis lanceolata. Korean J. Nutr. 31: 1076-1081 (1998)
  14. Higuchj M., Higashi N, Taki H, Osawa T. Cytolytic mechanisms of activated macrophages. Tumor necrosis factor and L-arginine dependent mechanisms act as synergistically as the major cytolytic mechanisms of activated macrophages. J. Immunol. 144: 1425-1431 (1990)
  15. McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxides in islet inflammation and diabetes. Proc. Soc. Exp. Biol. Med. 211: 24-32 (1996) https://doi.org/10.3181/00379727-211-43950D
  16. Cetkovic-Cvrlje M, Eizirik DL. TNF- and IFN-$\gamma$ potentiate the deleterious effects of IL-1$\beta$ on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine 6: 399-406 (1994) https://doi.org/10.1016/1043-4666(94)90064-7
  17. Yoon CY, Shin DH, Hong CM, Lee WK, Jang DD, Cho JC, Ahn JK, Ahn DK, Lee MS. The suppressive effects of cortex mori on NO, TNF-$\alpha$ and IL-1 production by macrophage. Korean J. Vet. Publ. Hlth. 22: 3 (1998)
  18. Gross SS, Wolin MS. Nitric oxide: pathophysiological mechanisms. Annu. Rev. Physiol. 57: 737-769 (1995) https://doi.org/10.1146/annurev.ph.57.030195.003513
  19. Stuehr DJ. Mammalian nitric oxide synthase. Biochim. Biophys. Acta. 1411: 217-230 (1999) https://doi.org/10.1016/S0005-2728(99)00016-X
  20. Kroncke KD, Fehsel K, Kolb-Bachofen V. Inducible nitric oxide synthase in human diseases. Clin. Exp. Immunol. 113: 147-156 (1998) https://doi.org/10.1046/j.1365-2249.1998.00648.x
  21. Oshima H, Bartsch H. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat. Res. 305: 253-264 (1994) https://doi.org/10.1016/0027-5107(94)90245-3
  22. Oh JS, Im GY, Teong J, Lee HC, Chung SS. Effect of steroid hormone on the expression of cytokine genes in the peritoneal macrophages of mouse. J. Korean Cancer Assoc. 26: 607-617 (1994)
  23. Romero R, Avila C, Santhanam U, Sehagal PB. Amniotic fluid interleukin 6 in preterm labor-associated with infractional. J. Clin. Invest. 85: 1392-1408 (1990) https://doi.org/10.1172/JCI114583
  24. Kishimoto T. The biology of interleukin-6. Blood 74: 1-10 (1989)
  25. Hamiton TA, Adams DO. Molecular mechanisms of signal transduction in macrophage activation. Immunol. Today 8: 151-158 (1987) https://doi.org/10.1016/0167-5699(87)90145-9
  26. Paulnock DM. Macrophage activation by T cells. Cur. Opin. Immunol. 4: 344-349 (1992) https://doi.org/10.1016/0952-7915(92)90087-U
  27. Cybulsky MI, Movat HZ, Dinarello CA. Role of interleukin-1 and tumor necrosis factor in acute inflammation. Ann. Inst. Pasteur. Immunol. 138: 505-512 (1987) https://doi.org/10.1016/S0769-2625(87)80068-5
  28. Havell EA. Evidence that tumor necrosis factor has an important role in antibacterial resistance. J. Immunol. 143: 2894-2899 (1989)
  29. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen- specific adaptive immunity. Annu. Rev. Immunol. 13: 251- 276 (1995) https://doi.org/10.1146/annurev.iy.13.040195.001343