Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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IL-1Ra Elaboration by Colchicine Stimulation in Normal Human Bronchial Epithelial Cells

정상 인체 기관지 상피세포에서 콜히친의 Interleukin-1 수용체 길항제 생성자극

  • Lee, Jae Hyung (Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine) ;
  • Kim, Sang Heon (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Kim, Tae Hyung (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Sohn, Jang Won (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Yoon, Ho Joo (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Shin, Dong Ho (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Park, Sung Soo (Department of Internal Medicine, College of Medicine, Hanyang University)
  • 이재형 (을지의과대학교 을지병원 내과학교실) ;
  • 김상헌 (한양대학교 의과대학 내과학교실) ;
  • 김태형 (한양대학교 의과대학 내과학교실) ;
  • 손장원 (한양대학교 의과대학 내과학교실) ;
  • 윤호주 (한양대학교 의과대학 내과학교실) ;
  • 신동호 (한양대학교 의과대학 내과학교실) ;
  • 박성수 (한양대학교 의과대학 내과학교실)
  • Received : 2007.01.23
  • Accepted : 2007.07.20
  • Published : 2007.08.30
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Abstract

Background: Asthma is a syndrome that is characterized by a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Colchicine is an inexpensive and safe medication with unique anti-inflammatory properties. IL-1Ra (Interleukin-1 receptor antagonist) mediates the anti-inflammatory effect in human inflammatory diseases, including asthma. This study examined whether IL-1Ra mediates the anti-inflammatory effect of colchicine in normal human bronchial epithelial cells (NHBE), RAW 264.7 cells (murine macrophage cell line), and a mouse lung. Methods: NHBE, RAW 264.7 cells and BALB/c mice were stimulated with colchicine, and the increase in the IL-1Ra level was estimated by ELISA, Western analysis and RT-PCR analysis. Results: Colchicine stimulated NHBE and RAW 264.7 cells to release IL-1Ra into the supernatant in a dose-and time-dependent manner. The major isoform of IL-1Ra in NHBE and RAW 264.7 cells is type I icIL-1Ra, and sIL-1Ra, respectively. IL-1Ra up-regulation was blocked by PD98059, a specific inhibitor in MAPK pathways. Colchicine also stimulated the secretion of IL-1Ra into the bronchoalveolar lavage (BAL) fluid of BALB/c mouse. Conclusion: Colchicine stimulates an increase in the IL-1Ra level both in vivo and in vitro, and might have an anti-inflammatory effect.

연구배경: 천식은 기류장애, 기도과민성 및 기도염증을 특징으로 하는 질환이다. 콜히친은 안전하고 저렴한 항염증 면역조절제로서 천식치료에 효과가 있다는 보고가 있으며, IL-1Ra는 천식을 포함한 인체 내 염증질환에 있어 항염증효과를 매개하는 대표적인 물질이다. 본 연구에서는 기도 내에서 콜히친에 의한 항염증작용이 IL-1Ra에 의해 매개될 수 있다는 가설을 세우고 이를 실험적으로 증명하고자 하였다. 방법: 정상 인체 기관지 상피세포와 RAW 264.7 세포, BALB/c 쥐에게 콜히친을 투여한 후 IL-1Ra의 생성을 ELISA, Western분석, RT-PCR 을 통해 측정하였다. 결과: 정상 인체 기관지 상피세포에서 콜히친의 투여농도가 증가함에 따라, 또한 투여 후 시간이 지남에 따라 IL-1Ra의 생성이 증가하였다. 이러한 IL-1Ra의 증가는 대표적인 MAPK경로 억제제인 PD98059에 의해 억제되었다. 콜히친의 IL-1Ra 자극효과는 BALB/c 쥐의 기관지 폐포세척액과 폐조직에서도 관찰되었다. 결론: 기도에서 콜히친은 생체 내와 생체 외에서 IL-1Ra의 생성을 유도하고 IL-1Ra를 통한 항염증 작용을 할 것으로 보이며, 적어도 콜히친에 의한 IL-1Ra의 생성에는 MAPK경로가 관여할 것으로 사료된다.

Keywords

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