생명과학회지 (Journal of Life Science)

한국생명과학회 (Korean Society of Life Science)
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Myristicin이 Ovalbumin으로 유도한 천식 생쥐모델에서 Th1/Th2 Balance를 조절하는 GATA-3에 미치는 효과

GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma

  • 이규 (부산대학교 의학전문대학원 미생물학과, 국가지정 수지상 세포 분화조절 연구) ;
  • 이창민 (부산대학교 의학전문대학원 미생물학과, 국가지정 수지상 세포 분화조절 연구실) ;
  • 정인덕 (부산대학교 의학전문대학원 미생물학과, 국가지정 수지상 세포 분화조절 연구실) ;
  • 정영일 (국가지정 수지상 세포 분화조절 연구실,부산대학교 자연과학대학 미생물학과) ;
  • 천성학 (국가지정 수지상 세포 분화조절 연구실) ;
  • 박희주 (부산대학교 의과대학 소아과) ;
  • 최일환 (인제대학교 의과대학 미생물학교실) ;
  • 안순철 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 신용규 (중앙대학교 의과대학 약리학교실) ;
  • 이상율 (부산대학교 의학전문대학원 생화학교실) ;
  • 염석란 (부산대학교 의과대학 응급의학과) ;
  • 김종석 (전북대학교 의학전문대학원 생화학교실) ;
  • 박영민 (부산대학교 의학전문대학원 미생물학과, 국가지정 수지상 세포 분화조절 연구)
  • Lee, Kyu (Department of Microbiology and Immunology, Pusan National University College of Medicine, National Research Laboratory Of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine) ;
  • Lee, Chang-Min (Department of Microbiology and Immunology, Pusan National University College of Medicine, National Research Laboratory Of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine) ;
  • Jung, In-Duk (Department of Microbiology and Immunology, Pusan National University College of Medicine, National Research Laboratory Of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine) ;
  • Jeong, Young-Il (National Research Laboratory Of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine, Department of Microbiology, Pusan National University College of Nature Science) ;
  • Chun, Sung-Hak (National Research Laboratory Of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine) ;
  • Park, Hee-Ju (Department of Pediatrics, Pusan National University College of Medicine) ;
  • Choi, Il-Whan (Department of Microbiology, Inje University College of Medicine) ;
  • Ahn, Soon-Cheol (Department of Microbiology and Immunology, Pusan National University College of Medicine) ;
  • Shin, Yong-Kyoo (Department of Pharmacology, Chungang University College of Medicine) ;
  • Lee, Sang-Yull (Department of Biochemistry, Pusan National University college of Medicine) ;
  • Yeom, Seok-Ran (Department of Emergency Medicine, Pusan National University college of Medicine) ;
  • Kim, Jong-Suk (Department of Biochemistry, Chonbuk National University Medical School) ;
  • Park, Yeong-Min (Department of Microbiology and Immunology, Pusan National University College of Medicine, National Research Laboratory Of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine)
  • 발행 : 2007.08.30
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초록

Myristicin은 육두구에서 발견되는 고농축 정유 중 하나인 물질이다. 하지만 Th1/Th2 면역반응에서 육두구의 항알레르기 효과는 아직 밝혀지지 않았다. 최근에 Th1/Th2 전사인자로서 T-bet, GATA-3가 밝혀졌는데 이번 실험에서 myristicin이 ovalbumin(OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1,Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다. 또한 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 myristicin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 myristicin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 myristicin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다.

Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

키워드

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