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KSBB Journal v.25 no.1, 2010년, pp.11 - 17  

혈관내피세포에서 트롬빈이 TNF-$\alpha$에 의해 유도되는 IL-6에 미치는 영향
Effect of Thrombin on the TNF-$\alpha$ Induced IL-6 Production in HUVECs

배종섭    (대구한의대학교 한방산업대학 한방제약공학과   ); 박문기    (대구한의대학교 한방산업대학 한방제약공학과  );
  • 초록

    본 논문에서는 혈관내피세포에서 저농도의 트롬빈이 TNF- $\alpha$ 가 NF-kB의 활성화를 통해 생성되는 IL-6의 생성량에 미치는 영향을 관찰하였다. TNF- $\alpha$ 는 혈관내피세포에서 NF-kB의 활성화를 통해 염증을 유발시킨다는 것은 잘 알려진 사실이다. 이 논문에서는 TNF- $\alpha$ 가 매개하는 염증작용에서 저농도의 트롬빈은 TNF- $\alpha$ 가 생성시키는 IL-6의 생성량을 감소시켰고, 여기에는 트롬빈의 수용체인 PAR-1이 작용하다는 것을 확인하였다. 뿐만 아니라, 세포내의 PI3-Kinase 역시 저농도 트롬빈이 관여한다는 것을 확인하였다. 이것은 저농도의 트롬빈이 수용체인 PAR-1을 활성화시키고, 활성화된 PAR-1 은 PI3-Kinase의 활성화을 통해 항염증작용을 보여준디는 것을 의미한다. 이 결과는 향후 중증 패혈증 및 각종 염증질환을 치료할 수 있는 신약개발에 있어 중요한 단서를 제공하고 혈관내피세포에서 아직 명확하게 밝혀지지 않은 트롬빈의 염증작용 및 항염증작용의 기전을 밝히는데 좋은 정보를 제공할 것이다.


    Here, we evaluated the effect of thrombin on the interleukin-6 production induced by tumor-necrosis-factor- $\alpha$ in endothelial cells. It is well known that tumor-necrosis-factor- $\alpha$ mediates inflammatory responses by activation of nuclear factor-kappa-B in endothelial cells. Here, we showed that lower concentration of thrombin decreased the production of interleukin-6 induced by tumor-necrosis-factor- $\alpha$ and this inhibitory effect of thrombin on interleukin-6 production was mediated by interacting with protease-activated-receptor-1. In addition, phosphoinositide-3-kinase was also involved the anti-inflammatory responses by lower concentration of thrombin in endothelial cells. These results suggested that lower concentration of thrombin mediated anti-inflammatory responses by interacting with protease-activated-receptor-1 on the cell membrane and phosphoinositide-3-kinase in the cell. These findings will provide the important evidence in the development of new medicine for the treatment of severe sepsis and inflammatory diseases and good clue for understanding unknown mechanisms by which thrombin showed the pro-inflammatory or anti-inflammatory activities in endothelial cells.


  • 주제어

    thrombin .   TNF- $\alpha$ .   HUVEC .   inflammation .   PAR-1.  

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