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

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

  • Park, Cheol (Blue-Bio Industry Regional Innovation Center, Dongeui University) ;
  • Choi, Yung-Hyun (Blue-Bio Industry Regional Innovation Center, Dongeui University)
  • 박철 (동의대학교 블루바이오 소재개발센터) ;
  • 최영현 (동의대학교 블루바이오 소재개발센터)
  • Published : 2009.10.30

Abstract

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.

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.

Keywords

References

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