생명과학회지 (Journal of Life Science)

  • 제18권2호
  • /
  • Pages.180-186
  • /
  • 2008
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

PMA에 의해 유도된 cycooxygenase-2 활성에 대한 새로운 발효법에 의한 대두산물의 억제 효능

Inhibition of Phorbol 12-myristate-13-acetate Induced Cyclooxygenase-2 Activity by Three-step Fermented Soybeans

  • 박철 (동의대학교 한의과대학 생화학교실 및 대학원 바이오물질제어학과(BK21)) ;
  • 이정옥 (경상대학교 농업생명과학대학 응용생명공학과) ;
  • 류충호 (경상대학교 농업생명과학대학 응용생명공학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 대학원 바이오물질제어학과(BK21))
  • Park, Cheol (Department of Biochemistry, Dongeui University College of Oriental Medicine) ;
  • Lee, Jeong-Ok (Division of Applied Life Science, Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Ryu, Chung-Ho (Division of Applied Life Science, Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine)
  • 발행 : 2008.02.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

이상의 연구 결과에 의하면 U937 세포에서 FSB 및 TFS 모두 2 mg/ml의 농도에서 6시간까지는 세포증식에 아무런 영향을 미치지 못하였고 PMA 처리에 의해서도 세포증식에는 변화가 없었으며, 세포의 형태 및 핵의 형태도 PMA와 FSB 및 TFS의 처리에 의해서 아무런 변화가 나타나지 않았다. 그러나 COX-2의 발현의 정도는 PMA 처리에 의해서 증가하였고, 이렇게 증가한 COX-2는 FSB 및 TFS의 선처리에 의해서 효과적으로 억제되는 것으로 나타났다 또한 COX-2에 의해 생성되어 염증반응을 유발하며 세포분열이나 증식에 영향을 줌으로서 각종 질병의 유발과 진행에 중요한 역할을 하는 것으로 알려져 있는 $PGE_2$의 경우도 PMA처리에 의하여 증가하였으며 FSB 및 TFS 처리에 의해서 강하게 억제되었다. 특히 FSB에 비하여 TFS를 선처리하였을 경우 PMA에 의하여 과발현된 COX-2 및 $PGE_2$ 생성의 억제정도가 더 강하게 나타났다. 이러한 결과는 FSB 및 TFS의 항염증기전 해석을 위한 이해와 향후 지속적인 연구를 위한 귀중한 자료가 될 것으로 사료된다.

In this study, we examined the effects of the fermented soybeans by Bacillus subtilis (FSB) and the novel three-step fermented soybeans (TFS) on the expression and activity of COX-2 in human leukemic U937 cell model. Treatment of phorbol 12-myristate 13-acetate (PMA) significantly induced pro-inflammatory mediators such as COX-2 expression and prostaglandin $E_2\;(PGE_2)$ production, whereas the levels of COX-1 remained unchanged. However, pre-treatment with FSB and TFS significantly attenuated the PMA-induced COX-2 protein as well as mRNA, which was associated with inhibition of $PGE_2$ production. Moreover, TFS exerts a much better inhibitory activity than FSB against PMA-induced activation of COX-2 and production of $PGE_2$ in U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of FSB and TFS.

키워드

참고문헌

  1. Balzary, R. W. and T. M. Cocks. 2006. Lipopolysaccharide induces epithelium- and prostaglandin E(2)-dependent relaxation of mouse isolated trachea through activation of cyclooxygenase (COX)-1 and COX-2. J. Pharmacol. Exp. Ther. 317, 806-812 https://doi.org/10.1124/jpet.105.097634
  2. Basta, S., S. Knoetig, A. Summerfield and K. C. McCullough. 2001. Lipopolysaccharide and phorbol 12-myristate 13- acetate both impair monocyte differentiation, relating cellular function to virus susceptibility. Immunology 103, 488-497 https://doi.org/10.1046/j.1365-2567.2001.01266.x
  3. Brown, J. R. and R. N. DuBois. 2004. Cyclooxygenase as a target in lung cancer. Clin. Cancer Res. 10, 4266s-4269s https://doi.org/10.1158/1078-0432.CCR-040014
  4. Brunelle, M., E. A. Sartin, L. G. Wolfe, J. Sirois and M. Dore. 2006. Cyclooxygenase-2 expression in normal and neoplastic canine mammary cell lines. Vet. Pathol. 43, 656-666 https://doi.org/10.1354/vp.43-5-656
  5. Chen, P., Y. Cai, Z. G. Yang, R. Zhou, G. S. Zhang, F. Domann and X. Fang. 2006. Involvement of PKC, p38 MAPK and AP-2 in IL-1$\beta$-induced expression of cyclooxygenase- 2 in human pulmonary epithelial cells. Respirology 11, 18-23 https://doi.org/10.1111/j.1440-1843.2006.00779.x
  6. Dempke, W., C. Rie, A. Grothey and H. J. Schmoll. 2001. Cyclooxygenase-2: a novel target for cancer chemotherapy? J. Cancer Res. Clin. Oncol. 127, 411-417 https://doi.org/10.1007/s004320000225
  7. FitzGerald, G. A. 2003. COX-2 and beyond: Approaches to prostaglandin inhibition in human disease. Nat. Rev. Drug Discov. 2, 879-890 https://doi.org/10.1038/nrd1225
  8. Giercksky, K. E. 2001. COX-2 inhibition and prevention of cancer. Best Pract. Res. Clin. Gastroenterol. 15, 821-833 https://doi.org/10.1053/bega.2001.0237
  9. Herschman, H. R. 1996. Prostaglandin synthase 2. Biochim. Biophys. Acta. 1299, 125-40 https://doi.org/10.1016/0005-2760(95)00194-8
  10. Heuze-Vourc'h, N., M. Liu, H. Dalwadi, F. E. Baratelli, L. Zhu, L. Goodglick, M. Pold, S. Sharma, R. D. Ramirez, J. W. Shay, J. D. Minna, R. M. Strieter and S. M. Dubinett. 2005. IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression. Biochem. Biophys. Res. Commun. 333, 470-475 https://doi.org/10.1016/j.bbrc.2005.05.122
  11. Jiang, Y. J., B. Lu, P. C. Choy and G. M. Hatch. 2003. Regulation of cytosolic phospholipase A2, cyclooxygenase- 1 and -2 expression by PMA, TNF$\alpha$, LPS and M-CSF in human monocytes and macrophages. Mol. Cell Biochem. 246, 31-38 https://doi.org/10.1023/A:1023495626568
  12. Jin, D. Z., L. L. Yin, X. Q. Ji and X. Z. Zhu. 2006. Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its expression. Eur. J. Pharmacol. 549, 166-172 https://doi.org/10.1016/j.ejphar.2006.07.055
  13. Johnson, A. C. 1996. Activation of epidermal growth factor receptor gene transcription by phorbol 12-myristate 13-acetate is mediated by activator protein 2. J. Biol. Chem. 271, 3033-3038
  14. Johnson, K. R., K. P. Becker, M. M. Facchinetti, Y. A. Hannun and L. M. Obeid. 2005. PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA). J. Biol. Chem. 277, 35257-35262 https://doi.org/10.1074/jbc.M203033200
  15. Ke, J., X. Long, Y. Liu, Y. F. Zhang, J. Li, W. Fang and Q. G. Meng. 2007. Role of NF-$\kappa B$ in TNF-$\alpha$-induced COX-2 expression in synovial fibroblasts from human TMJ. J. Dent. Res. 86, 363-367 https://doi.org/10.1177/154405910708600412
  16. Kim, S. O., K. S. Chun, J. K. Kundu and Y. J. Surh. 2004. Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF- $\kappa B$ and p38 MAPK in mouse skin. Biofactors 21, 27-31 https://doi.org/10.1002/biof.552210107
  17. Koki, A., N. K. Khan, B. M. Woerner, A. J. Dannenberg, L. Olson, K. Seibert, D. Edwards, M. Hardy, P. Isakson and J. L. Masferrer. 2002. Cyclooxygenase-2 in human pathological disease. Adv. Exp. Med. Biol. 507, 177-184 https://doi.org/10.1007/978-1-4615-0193-0_28
  18. Lee, E., M. K. Choi, Y. J. Lee, J. L. Ku, K. H. Kim, J. S. Choi and S. J. Lim. 2006. $\alpha$-tocopheryl succinate, in contrast to $\alpha$-tocopherol and $\alpha$-tocopheryl acetate, inhibits prostaglandin E2 production in human lung epithelial cells. Carcinogenesis 27, 2308-2315 https://doi.org/10.1093/carcin/bgl073
  19. Lee, J. O., M. H. Park, Y. H. Choi, Y. L. Ha and C. H. Ryu. 2007. New fermentation technique for complete digestion of soybean protein. J. Microbiol. Biotechn. 17, 1904-1907
  20. Nieminen, R., S. Leinonen, A. Lahti, K. Vuolteenaho, U. Jalonen, H. Kankaanranta, M. B. Goldring and E. Moilanen. 2005. Inhibitors of mitogen-activated protein kinases downregulate COX-2 expression in human chondrocytes. Mediators Inflamm. 5, 249-255
  21. Nishizuka, Y. 1995. Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 9, 484-496 https://doi.org/10.1096/fasebj.9.7.7737456
  22. Parekh, D. B., W. Ziegler and P. J. Parker. 2000. Multiple pathways control protein kinase C phosphorylation. EMBO J. 19, 496-503 https://doi.org/10.1093/emboj/19.4.496
  23. Reno, F. and M. Cannas. 2005. Effect of prostaglandin E2 on PMA-induced macrophage differentiation. Prostaglandins Other Lipid Mediat. 75, 13-24 https://doi.org/10.1016/j.prostaglandins.2004.08.001
  24. Sawaoka, H., S. Tsuji, M. Tsujii, E. S. Gunawan, Y. Sasaki, S. Kawano and M. Hori. 1999. Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab. Invest. 79, 1469-1477
  25. Seo, Y. J., M. S. Kwon, E. J. Shim, J. Y. Lee and H. W. Suh. 2006. The effects of phorbol 12-myristate 13-acetate, cholera toxin, prostaglandin E2 and norepinephrine on inducible nitric oxide synthase activation induced by lipopolysaccharide in C6 cells. Pharmacology 78, 178-184 https://doi.org/10.1159/000096349
  26. Soloff, M. S., D. L. Cook, Y. J. Jr, Jeng and G. D. Anderson. 2004. In situ analysis of interleukin-1-induced transcription of COX-2 and IL-8 in cultured human myometrial cells. Endocrinology 145, 1248-1254 https://doi.org/10.1210/en.2003-1310
  27. Thun, M. J., S. J. Henley and C. Patrono. 2002. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J. Natl. Cancer Inst. 94, 252-266 https://doi.org/10.1093/jnci/94.4.252
  28. Tong, M., Y. Ding and H. H. Tai. 2006. Reciprocal regulation of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase expression in A549 human lung adenocarcinoma cells. Carcinogenesis 27, 2170-2179 https://doi.org/10.1093/carcin/bgl053
  29. Yamamoto, Y. and R. B. Gaynor. 2001. Therapeutic potential of inhibition of the NF-$\kappa$B pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107, 135-142 https://doi.org/10.1172/JCI11914

피인용 문헌

  1. Inhibition of Cyclooxygenase-2 Activity and Prostaglandin E2Production through Down-regulation of NF-κB Activity by the Extracts of Fermented Beans vol.20, pp.3, 2010, https://doi.org/10.5352/JLS.2010.20.3.388