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MCP-1에 의해 유도된 THP-1 유주에 미치는 2-methoxy-1,4-naphthoquinone (MQ)의 영향

Effects of 2-methoxy-1,4-naphthoquinone (MQ) on MCP-1 Induced THP-1 Migration

  • 김시현 (세명대학교 임상병리학과) ;
  • 박보빈 (세명대학교 임상병리학과) ;
  • 홍성은 (세명대학교 임상병리학과) ;
  • 유성률 (세명대학교 임상병리학과) ;
  • 이장호 (세명대학교 임상병리학과) ;
  • 김사현 (세명대학교 임상병리학과) ;
  • 이평재 (세명대학교 바이오제약산업학부) ;
  • 조은경 (경운대학교 임상병리학과) ;
  • 문철 (세명대학교 임상병리학과)
  • Kim, Si Hyun (Department of Clinical Laboratory Science, Semyung University) ;
  • Park, Bo Bin (Department of Clinical Laboratory Science, Semyung University) ;
  • Hong, Sung Eun (Department of Clinical Laboratory Science, Semyung University) ;
  • Ryu, Sung Ryul (Department of Clinical Laboratory Science, Semyung University) ;
  • Lee, Jang Ho (Department of Clinical Laboratory Science, Semyung University) ;
  • Kim, Sa Hyun (Department of Clinical Laboratory Science, Semyung University) ;
  • Lee, Pyeongjae (School of Industrial Bio-Pharmaceutical Science, Semyung University) ;
  • Cho, Eun-Kyung (Department of Biomedical Laboratory Science, Kyungwoon University) ;
  • Moon, Cheol (Department of Clinical Laboratory Science, Semyung University)
  • 투고 : 2019.04.29
  • 심사 : 2019.05.22
  • 발행 : 2019.06.30

초록

본 연구는 2-methoxy-1,4-naphthoquinone (MQ)이 Monocyte chemoattractant protein-1 (MCP-1)에 의해 유도된 단구 유주에 미치는 효과를 알아보고자 진행되었다. 단구의 유주(migration) 현상은 신체 방어와 면역반응에 중요한 현상이다. MQ는 아시아권 국가에서 다양한 질병과 통증 치료에 민간요법으로 오랫동안 사용되었던 봉선화(Impatiens balsamina) 잎으로부터 추출한 주요 성분이다. 단구 세포주 THP-1를 이용하여 실험을 진행하였으며, MQ의 세포독성, MCP-1에 의해 유도된 유주 현상에 미치는 영향을 transwell system을 이용하여 확인하였다. MQ 작용기전을 이해하기 위해 cAMP 발현 및 Erk1/2 인산화를 각각 ELISA, Western-blot 기법을 통해 분석하였다. MQ의 단구 세포주 THP-1에 대한 MQ의 세포독성은 $10{\mu}M$ 농도에서 나타나기 시작했으며, $100{\mu}M$ 농도에서 약 50% 가량의 세포독성을 확인했다. 염증성 화학주성 인자 MCP-1에 의해 유도된 단핵구 세포주 THP-1의 유주현상은 MQ 처리 후 농도증가에 비례하여 증가하였으며, $0.1{\mu}M$ 농도의 MQ를 처리했을 때 가장 높은 증가를 보였다. MCP-1 단독 처리 시 감소하는 cAMP 의 배양액 내 발현은 MQ 동시 처리 시 더욱 감소하였고, 유주현상과 마찬가지로 $0.1{\mu}M$ 농도에서 가장 감소하였다. MCP-1의 수용체인 C-C motif chemokine receptor 2 (CCR2) 신호전달 과정에 관여하는 주요 신호전달 단백질인 Erk1/2의 인산화도 $0.1{\mu}M$ MQ 동시 처리 시 증가하였다. 이상의 결과를 통해 MQ가 MCP-1에 의해 유도되는 THP-1 세포주의 유주현상을 증가시키며, 연관된 cAMP 발현을 감소, Erk1/2 인산화는 증가시키는 경향을 확인하였다.

This study examined the effects of 2-methoxy-1,4-naphthoquinone (MQ) on the monocyte chemoattractant protein-1 (MCP-1)-induced migration of monocytes, which is an important phenomenon for the body defense and immune response. MQ is a major component extracted from Impatiens balsamina leaves, which have been used for many years in Asian medicine for the treatment of a range of diseases and pain. The cytotoxicity of MQ began to appear at a concentration of $10{\mu}M$, and approximately 50% cytotoxicity was confirmed at $100{\mu}M$. The MCP-1 induced migration of the THP-1 monocyte cell line increased after MQ treatment in a dose dependent manner and the largest increase was observed at $0.1{\mu}M$. The level of cAMP expression decreased after a treatment with $0.1{\mu}M$ MQ. The phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), a key signaling protein involved in the signaling pathway of C-C motif chemokine receptor 2 (CCR2), a receptor for MCP-1, was increased by the simultaneous treatment of $0.1{\mu}M$ MQ. These results show that MQ increases the MCP-1-induced migration of THP-1, decreases the level of cAMP expression, and increases the level of Erk1/2 phosphorylation.

키워드

참고문헌

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