Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Effects of Nuclear Factor-κB Decoy Oligodeoxynucleotide on Lipopolysaccharide-Induced Direct Acute Lung Injury

리포다당질로 인한 직접성 급성폐손상에서 Nuclear Factor-κB Decoy Oligodeoxynucleotide의 효과

  • Kim, Je Hyeong (Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital) ;
  • Yoon, Dae Wui (Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital) ;
  • Jung, Ki Hwan (Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital) ;
  • Kim, Hye Ok (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital) ;
  • Ha, Eun Sil (Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital) ;
  • Lee, Kyoung Ju (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital) ;
  • Hur, Gyu Young (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital) ;
  • Lee, Sung Yong (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital) ;
  • Lee, Sang Yeub (Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital) ;
  • Shin, Chol (Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital) ;
  • Shim, Jae Jeong (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital) ;
  • In, Kwang Ho (Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital) ;
  • Yoo, Se Hwa (Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital) ;
  • Kang, Kyung Ho (Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital)
  • 김제형 (고려대학교 의과대학 안산병원 호흡기내과) ;
  • 윤대위 (고려대학교 의과대학 안산병원 호흡기내과) ;
  • 정기환 (고려대학교 의과대학 안산병원 호흡기내과) ;
  • 김혜옥 (고려대학교 의과대학 구로병원 호흡기내과) ;
  • 하은실 (고려대학교 의과대학 안암병원 호흡기내과) ;
  • 이경주 (고려대학교 의과대학 구로병원 호흡기내과) ;
  • 허규영 (고려대학교 의과대학 구로병원 호흡기내과) ;
  • 이승룡 (고려대학교 의과대학 구로병원 호흡기내과) ;
  • 이상엽 (고려대학교 의과대학 안암병원 호흡기내과) ;
  • 신철 (고려대학교 의과대학 안산병원 호흡기내과) ;
  • 심재정 (고려대학교 의과대학 구로병원 호흡기내과) ;
  • 인광호 (고려대학교 의과대학 안암병원 호흡기내과) ;
  • 유세화 (고려대학교 의과대학 안암병원 호흡기내과) ;
  • 강경호 (고려대학교 의과대학 구로병원 호흡기내과)
  • Received : 2009.05.20
  • Accepted : 2009.07.02
  • Published : 2009.08.30
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Abstract

Background: The pathophysiologic mechanisms of early acute lung injury (ALI) differ according to the type of primary insult. It is important to differentiate between direct and indirect pathophysiologic pathways, and this may influence the approach to treatment strategies. NF-$\kappa$B decoy oligodeoxynucleotide (ODN) is a useful tool for the blockade of the expression of NF-$\kappa$B-dependent proinflammatory mediators and has been reported to be effective in indirect ALI. The purpose of this study was to investigate the effect of NF-$\kappa$B decoy ODN in the lipopolysaccharide (LPS)-induced direct ALI model. Methods: Five-week-old specific pathogen-free male BALB/c mice were used for the experiment. In the preliminary studies, tumor necrosis factor (TNF)-$\alpha$, interleukine (IL)-6 and NF-$\kappa$B activity peaked at 6 hours after LPS administration. Myeloperoxidase (MPO) activity and ALI score were highest at 36 and 48 hours, respectively. Therefore, it was decided to measure each parameter at the time of its highest level. The study mice were randomly divided into three experimental groups: (1) control group which was administered 50 ${\mu}L$ of saline and treated with intratracheal administration of 200 ${\mu}L$ DW containing only hemagglutinating virus of Japan (HVJ) vector (n=24); (2) LPS group in which LPS-induced ALI mice were treated with intratracheal administration of 200 ${\mu}L$ DW containing only HVJ vector (n=24); (3) LPS+ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 ${\mu}L$ DW containing 160 ${\mu}g$ of NF-$\kappa$B decoy ODN and HVJ vector (n=24). Each group was subdivided into four experimental subgroups: (1) tissue subgroup for histopathological examination for ALI at 48 hours (n=6); (2) 6-hour bronchoalveolar lavage (BAL) subgroup for measurement of TNF-$\alpha$ and IL-6 in BAL fluid (BALF) (n=6); (3) 36-hour BAL subgroup for MPO activity assays in BALF (n=6); and (4) tissue homogenate subgroup for measurement of NF-$\kappa$B activity in lung tissue homogenates at 6 hours (n=6). Results: NF-$\kappa$B decoy ODN treatment significantly decreased NF-$\kappa$B activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-$\alpha$ and interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score. Conclusion: NF-$\kappa$B decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.

Keywords

References

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