Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Role of Insulin in the Activation of $NF-{\kappa}B/I{\kappa}B$ Pathway in Macrophage Cells

대식세포주에서 인슐린이 $I{\kappa}B/NF-{\kappa}B$ 경로 활성화에 미치는 영향

  • Lee, Sang-Min (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Jang, Yeon-Sil (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) ;
  • Kim, Young-Whan (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Han, Sung-Koo (Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Shim, Young-Soo (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)
  • 이상민 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 장연실 (서울대학교 의과대학 내과학교실 및 의학연구원 폐연구소) ;
  • 이춘택 (분당서울대학교병원 폐센터, 내과) ;
  • 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)
  • Received : 2009.02.06
  • Accepted : 2010.02.12
  • Published : 2010.03.30
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Abstract

Background: Sepsis still has a high mortality rate despite adequate supportive care. Newer therapeutic modalities have been developed but they have generally ended in failure. Recently, insulin was reported to have an anti-inflammatory effect by inhibiting the $I{\kappa}B/NF-{\kappa}B$ pathway, and may have therapeutic potential in sepsis. However, the precise mechanism of the anti-inflammatory effect of insulin is unclear. This study examined the role of insulin in activating $I{\kappa}B/NF-{\kappa}B$ in macrophage. Methods: Raw 264.7 cells, a murine macrophage cell line, were used in this experiment. Western blotting using $I{\kappa}B$ Ab and phosphor-specific $I{\kappa}B$ Ab was performed to evaluate the degradation and phosphorylation of $I{\kappa}B$ cells. For the $I{\kappa}B$ Kinase (IKK) activity, an immune complex kinase assay was performed. The level of interleukin-6 (IL-6) was measured by ELISA to determine the level of proinflammatory cytokine. Results: $I{\kappa}B{\alpha}$ degradation began 30 min after lipopolysaccharide (LPS) treatment. However, an insulin pretreatment suppressed the $I{\kappa}B{\alpha}$ degradation caused by the LPS treatment. The phosphorylation of $I{\kappa}B{\alpha}$ and IKK activity was also inhibited by the insulin pretreatment. Finally, the insulin pretreatment showed a tendency to suppress the induction of IL-6 by LPS. Conclusion: Insulin might have an anti-inflammatory effect though partial inhibition of the $I{\kappa}B/NF{\kappa}B$ pathway in macrophage cell lines.

Keywords

References

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