Journal of Ginseng Research

  • 제33권4호
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  • Pages.330-336
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  • 2009
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  • 1226-8453(pISSN)
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  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
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Ginsenoside Rb1의 세포간 유착, 세포표면 단백질 발현 및 세포형태변화에 미치는 효과

Effect of Ginsenoside Rb1 on Cell Adhesion, Surface Molecule Expression and Morphological Changes

  • 김병훈 (강원대학교 BT학부대학 생명공학부 분자의생명공학) ;
  • 조재열 (강원대학교 BT학부대학 생명공학부 분자의생명공학)
  • Kim, Byung-Hun (School of Bioscience and Biotechnology, Kangwon National University) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology, Kangwon National University)
  • 발행 : 2009.12.31
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초록

G-Rb1에 의한 단핵구 세포주인 U937 세포와 대식세포주인 RAW264.7 세포의 유착조절 능, 세포표면 단백질 발현율 및 세포모양 변화능 조절효과를 조사하여 다음과 같은 결론을 얻었다. 1. G-Rb1은 CD29항체 (MEM101A) 및 CD43 항체(161-46) 처리에 의해 유도된 세포-세포간 유착현상을 20%에서 35%까지 유의적으로 상승하였다. 2. G-Rb1은 fibronectin처리에 의해 유도된 U937 세포-fibronectin간 유착현상을 상승시켰다. 3. G-Rb1은 CD29 및 CD43의 세포표면 발현 수준을 유의적으로 증가시켰으나 CD82의 발현은 억제시켰다. 4. G-Rb1은 PMA에 의해 유도된 형태변화는 촉진경향을 반면에 LPS에 의한 변화는 억제경향을 나타내었다. 인삼의 주요사포닌 성분인 G-Rb1의 약리작용이 활발히 연구되고 있다. 특별히, 본 화합물이 갖는 면역증강 및 항암 효능은 인삼이 갖는 이들 효과를 대신하는 것으로 보고 되어져 있다. 그러나, 세포유착과정이 다양한 염증과정, 알러지 반응 및 암세포의 이동과 전이성 등에 관련이 있다는 관점에서 볼 때 본 연구결과는 이들 약물이 갖는 치료기전을 설명하기에는 충분하지 않는 것으로 판단된다. 오히려, 본 결과는 G-Rb1이 특정 농도 ($25-50\;{\mu}M$ 수준)에서 세포의 활성을 촉진할 수 있다는 가능성을 시사한다고 하겠다. 특별히, G-Rb1의 세포유착 촉진 기능에 관한 기전 이해를 위해, 이후, 세포유착 유도 신호전달 단백질의 활성을 포함한 다양한 분자적 수준에서의 추가적인 실험들을 진행하고 한다.

Cell-cell adhesion managed by various adhesion molecules is known to be one of important phenomena found in numerous immunological responses or diseases such as immunostimulation, rheumatoid arthritis and allergic diseases. In this study, we examined the regulatory role of ginsenosides (G)-Rb1, reported to display immunostimulatory and anticancer effects, on cell adhesion, the up-regulation of surface adhesion molecules and morphological changes using monocytic U937 and macrophage-like RAW264.7 cells. G-Rb1 significantly up-regulated U937 cell-cell adhesion mediated by both CD29 and CD43. It also enhanced U937 cell-fibronectin adhesion, while CD29 blocking antibody P5D2 strongly suppressed it. In agreement, this compound also significantly increased the surface level of CD29 as well as CD43. Furthermore, this compound differentially modulated CD82 up-regulation and morphological changes triggered by lipopolysaccharide (LPS) and phorbol-12-myristate-13-acetate (PMA). Therefore, these results suggest that G-Rb1 may have differential modulatory function on cell adhesion events, surface molecule expression and morphological changes responsible for immune responses.

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참고문헌

  1. Murtaugh MP, Foss DL. Inflammatory cytokines and antigen presenting cell activation. Vet Immunol Immunopathol 87: 109-121 (2002) https://doi.org/10.1016/S0165-2427(02)00042-9
  2. Caulfield JJ, Fernandez MH, Sousa AR, Lane SJ, Lee TH, Hawrylowicz CM. Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids. Immunology 98: 104-110 (1999) https://doi.org/10.1046/j.1365-2567.1999.00862.x
  3. Woods ML, Shimizu Y. Signaling networks regulating beta1 integrin-mediated adhesion of T lymphocytes to extracellular matrix. J Leukoc Biol. 69: 874-880 (2001)
  4. Keibel A, Singh V, Sharma MC. Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des. 15: 1949-1955 (2009) https://doi.org/10.2174/138161209788453167
  5. Van Waes C. Cell adhesion and regulatory molecules involved in tumor formation, hemostasis, and wound healing. Head Neck 17: 140-147 (1995) https://doi.org/10.1002/hed.2880170212
  6. Skubitz AP. Adhesion molecules. Cancer Treat Res. 107: 305-329 (2002)
  7. Sheibani N, Frazier WA. Thrombospondin-1, PECAM-1, and regulation of angiogenesis. Histol Histopathol. 14: 285-294 (1999)
  8. Yusuf-Makagiansar H, Anderson ME, Yakovleva TV, Murray JS, Siahaan TJ. Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases. Med Res Rev. 22: 146-167 (2002) https://doi.org/10.1002/med.10001
  9. Yun TK, Lee YS, Lee YH, Kim SI, Yun HY. Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J Korean Med Sci 16 Suppl: S6-18 (2001)
  10. Choi KT. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer. Acta Pharmacol Sin. 29: 1109-1118 (2008)
  11. Kim BH, Lee YG, Park TY, Kim HB, Rhee MH, Cho JY. Ginsenoside Rp1, a ginsenoside derivative, blocks lipopolysaccharide-induced interleukin-1beta production via suppression of the NF-kappaB pathway. Planta Med. 75: 321-326 (2009) https://doi.org/10.1055/s-0028-1112218
  12. Hasegawa H, Uchiyama M. Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite. Planta Med. 64: 696-700 (1998) https://doi.org/10.1055/s-2006-957560
  13. Luo YM, Cheng XJ, Yuan WX. Effects of ginseng root saponins and ginsenoside Rb1 on immunity in cold water swim stress mice and rats. Zhongguo Yao Li Xue Bao 14: 401-404 (1993)
  14. Hu S, Concha C, Lin F, Persson Waller K. Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle. Vet Immunol Immunopathol. 91: 29-37 (2003) https://doi.org/10.1016/S0165-2427(02)00264-7
  15. Wang CZ, Xie JT, Zhang B, Ni M, Fishbein A, Aung HH, Mehendale SR, Du W, He TC, Yuan CS. Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells. Int J Oncol. 31: 1149-1156 (2007)
  16. Chai H, Wang Q, Huang L, Xie T, Fu Y. Ginsenoside Rb1 inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Biol Pharm Bull. 31: 2050-2056 (2008) https://doi.org/10.1248/bpb.31.2050
  17. Cho JY, Yoo ES, Baik KU, Park MH, Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Med. 67: 213-218 (2001) https://doi.org/10.1055/s-2001-12005
  18. Cho JY, Fox DA, Horejsi V, Sagawa K, Skubitz KM, Katz DR, Chain B. The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood 98: 374-382 (2001) https://doi.org/10.1182/blood.V98.2.374
  19. Larrucea S, Gonzalez-Rubio C, Cambronero R, Ballou B, Bonay P, Lopez-Granados E, Bouvet P, Fontan G, Fresno M, Lopez-Trascasa M. Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement. J Biol Chem. 273: 31718-31725 (1998) https://doi.org/10.1074/jbc.273.48.31718
  20. Cho JY, Katz DR, Chain BM. Staurosporine induces rapid homotypic intercellular adhesion of U937 cells via multiple kinase activation. Br J Pharmacol. 140: 269-276 (2003) https://doi.org/10.1038/sj.bjp.0705436
  21. Cho JY, Chain BM, Vives J, Horejsi V, Katz DR. Regulation of CD43-induced U937 homotypic aggregation. Exp Cell Res. 290: 155-167 (2003) https://doi.org/10.1016/S0014-4827(03)00322-7
  22. Cho JY, Kim AR, Joo HG, Kim BH, Rhee MH, Yoo ES, Katz DR, Chain BM, Jung JH. Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions. Biochem Biophys Res Commun. 313: 954-961 (2004) https://doi.org/10.1016/j.bbrc.2003.12.026
  23. Matsumoto M, Shigeta A, Miyasaka M, Hirata T. CD43 plays both antiadhesive and proadhesive roles in neutrophil rolling in a context-dependent manner. J Immunol. 181: 3628-3635 (2008)
  24. Cho JY. Chloroquine, an anti-malarial agent, acts as a novel regulator of beta 1-integrin-mediated cell-cell adhesion. Biol Pharm Bull. 31: 726-730 (2008) https://doi.org/10.1248/bpb.31.726
  25. Cordes N, Park CC. beta1 integrin as a molecular therapeutic target. Int J Radiat Biol. 83: 753-760 (2007) https://doi.org/10.1080/09553000701639694
  26. Kawahira K, Sumiyoshi M, Sakanaka M, Kimura Y. Effects of ginsenoside Rb1 at low doses on histamine, substance P, and monocyte chemoattractant protein 1 in the burn wound areas during the process of acute burn wound repair. J Ethnopharmacol. 117: 278-284 (2008) https://doi.org/10.1016/j.jep.2008.01.032
  27. Deane JA, Hickey MJ. Molecular mechanisms of leukocyte trafficking in T-cell-mediated skin inflammation: insights from intravital imaging. Expert Rev Mol Med. 11: e25 (2009) https://doi.org/10.1017/S146239940900115X

피인용 문헌

  1. Ethanolic fermentation from red ginseng extract using Saccharomyces cerevisiae and Saccharomyces carlsbergensis vol.20, pp.1, 2011, https://doi.org/10.1007/s10068-011-0018-5