Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Expression of COX-2 and IDO by Uteroglobin Transduction in NSCLC Cell Lines

비소세포폐암 세포주에서 Uteroglobin Transduction이 COX-2 및 IDO의 발현에 미치는 영향

  • Park, Gun Min (Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine) ;
  • Lee, Sang-Min (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Yim, Jae-Joon (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Yang, Seok-Chul (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Yoo, Chul Gyu (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Lee, Choon-Taek (Respiratory Center, Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Han, Sung Koo (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Sim, Young-Soo (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Kim, Young Whan (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine)
  • 박근민 (동국대학교 의과대학 동국대학교 일산병원 내과) ;
  • 이상민 (서울대학교 의과대학 내과학교실 및 폐연구소) ;
  • 임재준 (서울대학교 의과대학 내과학교실 및 폐연구소) ;
  • 양석철 (서울대학교 의과대학 내과학교실 및 폐연구소) ;
  • 유철규 (서울대학교 의과대학 내과학교실 및 폐연구소) ;
  • 이춘택 (분당서울대학교병원 폐센터, 내과) ;
  • 한성구 (서울대학교 의과대학 내과학교실 및 폐연구소) ;
  • 심영수 (서울대학교 의과대학 내과학교실 및 폐연구소) ;
  • 김영환 (서울대학교 의과대학 내과학교실 및 폐연구소)
  • Received : 2009.02.11
  • Accepted : 2009.03.18
  • Published : 2009.04.30
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Abstract

Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-$\gamma$) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-$\gamma$ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

연구배경: Uteroglobin (UG)은 폐를 비롯한 우리 몸의 대부분의 표피세포에서 생성되는 면역조절능을 가진 분비단백이다. UG의 과발현은 cyclooxygenase (COX)-2의 발현의 감소 및 암세포의 성장억제와 관련이 있다. Indoleamine 2,3-dioxygenase (IDO)는 kynurenine pathway를 통해 tryptophan을 이화시키는 효소로서, 국소적으로 tryptopha을 고갈시키고 tryptophan 대사물을 생성 함으로써 T 세포의 면역반응을 억제시키는 데 기여한다. 방 법: 본 연구에서는 여러 비소세포폐암 세포주, 특히 A549에서 COX-2와 IDO의 발현양상 및 UG transduction 이 COX-2 및 IDO의 발현에 미치는 영향을 살펴보았다. 결 과: A549와 H460에서 구조적으로 COX-2와 IDO가 모두 발현되었고, COX-2 및 IDO의 발현은 UG transduction에 의해 감소되었다. A549에 IFN-$\gamma$를 투여했을때 COX-2 및 IDO의 발현이 약간 증가하였고, 이는 UGtransduction 시행 후 다시 감소하였다. 그러나, A549에 UG transduction 시행하여 감소된 COX-2, IDO의 발현은 IFN-$\gamma$ 투여 후에도 증가하지 않았다. A549 COX-2 sense와 A549 COX-2 anti-sense (siRNA 감염) 세포주 모두에서 COX-2의 발현여부와 상관없이 IDO가 발현되었고, UG transduction으로 인해 IDO의 발현이 감소하였다. 결 론: 이러한 결과는 UG의 세포성장억제 기능이 COX-2를 통한 기전과는 독립적으로 IDO의 면역관용 기전과 관련될 가능성이 있음을 시사한다.

Keywords

References

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