Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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The Effects of Phenethyl Isothiocyanate on Nuclear Factor-κB Activation and Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression Induced by Toll-like Receptor Agonists

Phenethyl Isothiocyanate가 Toll-like Receptor Agonists에 의해 유도된 Nuclear Factor-κB 활성과 Cyclooxygenase-2, Inducible Nitric Oxide Synthase 발현에 미치는 효과

  • Kim, Soo-Jung (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Park, Hye-Jeong (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Shin, Hwa-Jeong (Department of Medical Science, College of Medical Sciences, SoonChunHyang University) ;
  • Kim, Ji-Soo (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Ahn, Hee-Jin (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Min, In-Soon (Department of Healthcare Management, College of Medical Sciences, SoonChunHyang University) ;
  • Youn, Hyung-Sun (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University)
  • 김수정 (순천향대학교 의료과학대학 임상병리학과) ;
  • 박혜정 (순천향대학교 의료과학대학 임상병리학과) ;
  • 신화정 (순천향대학교 의료과학대학 의료과학과) ;
  • 김지수 (순천향대학교 의료과학대학 임상병리학과) ;
  • 안희진 (순천향대학교 의료과학대학 임상병리학과) ;
  • 민인순 (순천향대학교 의료과학대학 보건행정경영학과) ;
  • 윤형선 (순천향대학교 의료과학대학 임상병리학과)
  • Received : 2011.09.30
  • Accepted : 2011.11.02
  • Published : 2011.12.31
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Abstract

Toll-like receptors (TLRs) play an important role in induction of innate immune responses. The activation of TLRs triggers inflammatory responses that are essential for host defense against invading pathogens. Phenethyl isothiocyanate (PEITC) extracted from cruciferous vegetables has an effect on anti-inflammatory therapy. Dysregulated activation of nuclear factor-${\kappa}$B (NF-${\kappa}$B), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) has been shown to play important roles in the development of certain inflammatory disease. To evaluate the therapeutic potential of PEITC, NF-${\kappa}$B activation and COX-2 and iNOS expression induced by lipopolysaccharide (LPS, TLR4 agonist), polyinosinic-polycytidylic acid (Poly[I:C], TLR3 agonist), 2 kDa macrophageactivating lipopeptide (MALP-2, TLR2 and TLR6 agonist) or oligodeoxynucleotide 1668 (ODN1668, TLR9 agonist) were examined. PEITC inhibits the activation of NF-${\kappa}$B induced by LPS or Poly[I:C] but not by MALP-2 or ODN1668. PEITC also suppressed the iNOS expression induced by LPS or Poly[I:C]. However, PEITC did not suppress COX-2 expression induced by LPS, Poly[I:C], MALP-2, or ODN1668. These results suggest that PEITC has the specific mechanism for antiinflammatory responses.

염증의 중요한 분자학적 기전에는 cyclooxygenase-2 (COX-2)에 의한 prostaglandins (PGs) 생성과 inducible nitric oxide synthase (iNOS)에 의한 nitric oxide (NO) 생성이 있다. 많은 종류의 박테리아나 바이러스가 전사요소인 nuclear factor-${\kappa}$B(NF-${\kappa}$B)를 활성화시켜 여러 타깃 유전자의 발현을 조절해 PGs나 NO와 같은 염증물질을 유도하게 된다. 우리는 이번 실험을 통하여 phenethyl isothiocyanate (PEITC)가 toll-like receptor(TLR) agonists에 의해 유도된 NF-${\kappa}$B활성과 COX-2, iNOS 발현에 어떠한 영향을 미치는지 알아 보았다. PEITC는 lipopolysaccharide (LPS)와 polyinosinic-polycytidylic acid (poly[I:C])에 의해 유도된 NF-${\kappa}$B활성을 억제시켰다. 또한 PEITC는 LPS와 Poly[I:C]에 의해 유도된 iNOS의 발현도 억제시켰다. 하지만 PEITC는 TLR agonists들인 LPS, Poly[I:C], 2 kDa macrophage-activating lipopeptide (MALP-2), oligodeoxynucleotide 1668 (ODN1668)에 의한 COX-2 발현은 억제시키지 못하였다. 즉 PEITC가 TRIF-dependent 신호전달체계만을 조절하여 TRIF-dependent 신호전달체계에 의해 조절되는 iNOS는 억제하지만 MyD88-dependent 신호전달 체계에 의해 조절되는 COX-2는 억제하지 못한다는 것을 설명해준다. 이러한 결과는 iNOS와 COX-2가 서로 다른 메커니즘에 의해 조절된다는 것을 암시하며, PEITC가 여러 병원균들로부터 유도되는 염증반응이나 만성적인 질병들을 조절할 수 있음을 제시하는 중요한 결과이다.

Keywords

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