The Effects of Nuclear Factor-κB Decoy Oligodeoxynucleotide on Lipopolysaccharide-Induced Direct Acute Lung Injury

서지정보

· 발행기관 : 대한결핵및호흡기학회
· 수록지 정보 : Tuberculosis and Respiratory Diseases / 67권 / 2호 / 95 ~ 104페이지
· 저자명 : 김제형, 허규영, 이승룡, 이상엽, 신철, 심재정, 인광호, 유세화, 윤대위, 정기환, 김혜옥, 하은실, 이경주, 강경호

초록

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-κB decoy oligodeoxynucleotide (ODN) is a useful tool for the
blockade of the expression of NF-κB-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-κB 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)-α, interleukine (IL)-6 and NF-κB 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 μL of saline and treated with intratracheal administration of 200 μL 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 μL DW containing only HVJ vector (n=24); (3) LPS＋ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 μL DW containing 160 μg of NF-κB 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-α 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-κB activity in lung tissue homogenates at 6 hours (n=6).
Results: NF-κB decoy ODN treatment significantly decreased NF-κB activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-α and
interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score.
Conclusion: NF-κB decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.

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