생명과학회지 (Journal of Life Science)

  • 제19권10호
  • /
  • Pages.1396-1402
  • /
  • 2009
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

PMA에 의한 cyclooxygenase-2 발현 및 prostaglandin E2의 생성 증가에 미치는 톳 추출물의 영향

Hizikia fusiforme Inhibits Cyclooxygenase-2 Expression and Prostaglandin E2 Production by PMA through Inactivation of NF-κB

  • 박철 (동의대학교 블루바이오 소재개발센터) ;
  • 최영현 (동의대학교 블루바이오 소재개발센터)
  • Park, Cheol (Blue-Bio Industry Regional Innovation Center, Dongeui University) ;
  • Choi, Yung-Hyun (Blue-Bio Industry Regional Innovation Center, Dongeui University)
  • 발행 : 2009.10.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

본 연구에서는 갈조류의 일종인 톳(H. fusiforme)의 항염증 효과에 관한 생화학적 기전 해석을 위하여 U937 단핵구 세포를 이용하였으며, PMA에 의하여 인위적으로 유발된 COX-2의 발현 및 $PGE_2$의 생성 증가에 미치는 몇 가지 톳 추출물의 영향을 조사하였다. PMA는 U937 세포에서 처리 농도 의존적으로 COX-2의 전사 및 번역수준의 발현을 증가시켰으나, COX-1의 발현에는 큰 변화가 없었다. PAM에 의한 COX-2의 발현 증가는 $PGE_2$ 생성 증가와 연관성이 있었고, 톳의 열수 추출물에 비하여 에탄올 및 메탄올 추출물은 COX-2의 발현 증가는 $PGE_2$ 생성 증가를 매우 억제시켰으나, COX-1의 발현에는 영향을 주지 않았다. 아울러 PMA에 의한 NF-$\kappa$B의 핵내 이동 및 I$\kappa$B의 분해를 톳의 에탄올 및 메탄올 추출물이 완벽하게 차단시켰다. 본 연구의 결과는 톳의 에탄올 및 메탄올 추출물이 NF-$\kappa$B의 활성을 차단함으로서 COX-2의 발현 및 $PGE_2$ 생성을 저해하였음을 의미하며, 이는 톳이 강력한 항염증 효능을 가지고 있음을 뒷받침하여 주는 것이다.

Hizikia fusiforme is a kind of edible brown seaweed that grows mainly in the northwest Pacific including Korea, Japan and China, and has been widely used as food in Korea. Induction of cyclooxygenase-2 (COX-2) expression and prostaglandin $E_2$ ($PGE_2$) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In this study, we investigated the effects of extracts of H. fusiforme on the expression of COX-2 and production of $PGE_2$ in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate 13-acetate (PMA) to mimic inflammation, methanol extract of H. fusiforme (MEHF) and ethanol extract of H. fusiforme (EEHF), but not water extract of H. fusiforme (WEHF), inhibited PMA-induced expression of both COX-2 protein and mRNA, which was associated with inhibition of $PGE_2$ production. To investigate the mechanism by which MEHF and EEHF inhibit COX-2 gene expression and $PGE_2$ production, we examined the activation of nuclear factor-kappaB (NF-$\kappa$B) in U937 cells. Pre-treatment with MEHF and EEHF significantly attenuated the PMA-induced IkappaB degradation and prevented nuclear translocation of NF-$\kappa$B. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of H. fusiforme.

키워드

참고문헌

  1. Bamba, H, S. Ota, A Kato, C. Kawamoto, and K Fujiwara. 2000. Prostaglandins up-regulate vascular endothelial growth factor production through distinct pathways in differentiated U937 cells. Biochem. Biaphys. Res. Commun. 273, 485-491 https://doi.org/10.1006/bbrc.2000.2969
  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. Botting, R. M. 2006. Inhibitors of cyclooxygenases: mechanisms, selectivity and uses. J. Physiol. Phannacol. 5, S113-124
  4. Claria, J. 2006. Regulation of cell proliferation and apoptosis by bioactive lipid mediators. Recent Pat. Anticancer Drug Discov. 1, 369-382 https://doi.org/10.2174/157489206778776961
  5. 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
  6. Devesa, V., D. Velez, and R. Montoro. 2008. Effect of thermal treatments on arsenic species contents in food. Food Chem. Toxicol. 46, 1-8 https://doi.org/10.1016/j.fct.2007.08.021
  7. Dobashi, K, T. Nishino, M. Fujihara, and T. Nagumo. 1989. Isolation and preliminary characterization of fucose-containing sulfated polysaccharides with blood-anticoagulant activity from the brown seaweed Hizikia fusiforme. Carbohydr. Res. 194, 315-320 https://doi.org/10.1016/0008-6215(89)85032-3
  8. Goetz, C. A and A S. Baldwin. 2008. NF-kappaB pathways in the immune system: control of the germinal center reaction. Immunol. Res. 41, 233-247 https://doi.org/10.1007/s12026-008-8033-1
  9. Gonzalez-Periz, A and J. Claria. 2007. New approaches to the modulation of the cyclooxygenase-2 and 5-lipoxygenase pathways. Curro Top. Med. Chem. 7, 297-309 https://doi.org/10.2174/156802607779941378
  10. Guzik, T. J., R. Korbut, and T. Adamek-Guzik. 2003. Nitric oxide and superoxide in inflammation and immune regulation. J. Physiol. Pharmacol. 54, 469-487
  11. Hoffmann, A, G. Natoli, and G. Ghosh. 2006. Transcriptional regulation via the NF-kappaB signaling module. Oncogene 25, 6706-6716 https://doi.org/10.1038/sj.onc.1209933
  12. 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
  13. Jung, K, E. Ha, Y. Uhm, H Park, M. J. Kim, H. Kim, H Baik, M. Hong, J. Yang, and S. V. Yim. 2007. Suppressive effect by Hizikia fusiforme on theproduction of tumor necrosis factor in BV2 murine microglial cells. Neurol. Res. 29, S88-92 https://doi.org/10.1179/016164107X172383
  14. Li, B., X. J. Wei, J. 1. Sun, and S. Y. Xu. 2006. Structural investigation of a fucoidan containing a fucose-free core from the brown seaweed, Hizikia fusiforme. Carbohydr. Res. 341, 1135-1146 https://doi.org/10.1016/j.carres.2006.03.035
  15. Murakami, M. and I. Kudo. 2004. Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway. Prog. Lipid. Res. 43, 3-35 https://doi.org/10.1016/S0163-7827(03)00037-7
  16. Patel, T. N., M. H. Shishehbor, and D. L. Bhatt. 2007. A review of high-dose statin therapy: targeting cholesterol and inflammation in atherosclerosis. Eur. Heart J. 28, 664-672 https://doi.org/10.1093/eurheartj/ehl445
  17. 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
  18. Surh, Y. J., K. S. Chun, H. H. Cha, S. S. Han, Y. S. Keum, K. K. Park, and S. S. Lee. 2001. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-$\kappa$B activation. Mutat. Res. 480, 243-268 https://doi.org/10.1016/S0027-5107(01)00183-X
  19. Vainio, H. 2001. Is COX-2 inhibition a panacea for cancer prevention? Int. J. Cancer 94, 613-614 https://doi.org/10.1002/ijc.1518
  20. Watanabe, T., T. Hirayama, T. Takahashi, T. Kokubo, and M. Ikeda. 1979. Toxicological evaluation of arsenic in edible seaweed, Hizikia species. Toxicology 14, 1-22 https://doi.org/10.1016/0300-483X(79)90088-X
  21. Wu, Z. H. and S. Miyamoto. 2007. Many faces of NF-kappaB signaling induced by genotoxic stress. J. Mol. Med. 85, 1187-1202 https://doi.org/10.1007/s00109-007-0227-9
  22. Wymann, M. P. and R. Schneiter. 2008. Lipid signalling in disease. Nat. Rev. Mol. Cell BioI. 9, 162-176 https://doi.org/10.1038/nrm2335