Attenuation of lung injury in allograft rejection using NF-κB decoy transfection - Novel strategy for use in lung transplantation

Kenichi Ohmori, Shin Ichi Takeda, Shinichiro Miyoshi, Masato Minami, Shigeru Nakane, Mitsunori Ohta, Yoshiki Sawa, Hikaru Matsuda

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-κB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-κB decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. Methods: Left lung transplantation was performed in pairs of Brown Norway (RT1 n) and Lewis (RT 1) rats. In Group NF (n=6), the allografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-κB decoy and preserved for 60 min at 4°C. A scramble decoy was used in the positive control (Group S, n=5) and simple PBS solution in the negative control (Group C, n=5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. Results: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445±162 vs 1305±123 ppb, P<0.02), while improvements in PaO2 (197±28 vs. 60±18 mmHg, P<0.02) and rejection score (1.8±0.3 vs. 2.5±0.4) were also observed. There were no differences in these parameters between Groups S and C. Conclusions: Inhibition of NF-κB activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings.

Original languageEnglish
Pages (from-to)23-27
Number of pages5
JournalEuropean Journal of Cardio-Thoracic Surgery
Volume27
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

Keywords

  • Allograft lung injury
  • Gene Transfer
  • Lung transplantation
  • NF-κB

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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