Effect of FK506 and Cyclosporin A on $I{\kappa}B{\alpha}$ Degradation and $IKK{\alpha}$ Pathway in Bronchial Epithelial Cells, Monocytes, Lymphocytes and Alveolar Macrophages

FK506과 cyclosporin A가 기관지상피세포, 단핵구, 림프구 및 폐포대식세포에서 $I{\kappa}B{\alpha}$ 분해 및 $IKK{\alpha}$ 활성에 미치는 효과

  • Yoon, Ho Il (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Lee, Chang-Hoon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Lee, Hee-Seok (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Lee, Choon-Taek (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Kim, Young Whan (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Han, Sung Koo (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Shim, Young-Soo (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University) ;
  • Yoo, Chul-Gyu (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Lung Institute, Medical Research Center, Seoul National University)
  • 윤호일 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 이창훈 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 이희석 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 이춘택 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 김영환 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 한성구 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 심영수 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 유철규 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소)
  • Published : 2003.04.30

Abstract

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

Acknowledgement

Supported by : 서울대학교병원