@article {LaiP656, author = {Yi-Ting Lai and Chang-Wei Lin and Chih-Hao Chang and Chung-Yuang Cheng and Wei-Han Lin and Li-Fu Li}, title = {Ventilation-induced neutrophil infiltration depends on nuclear factor-kB and NF-kB repressing factor}, volume = {42}, number = {Suppl 57}, elocation-id = {P656}, year = {2013}, publisher = {European Respiratory Society}, abstract = {Background and objective: High-tidal-volume mechanical ventilation used in patients with acute lung injury (ALI) can induce the release of inflammatory cytokines, recruitment of neutrophils, and disruption of alveolar epithelial and endothelial barriers. Nuclear factor-kB (NF-kB) and NF-kB repressing factor (NRF) have previously been shown to participate in the regulation of macrophage inflammatory protein-2 (MIP-2) during ALI. However, the mechanisms regulating interactions between mechanical ventilation and NF-kB/NRF remains unclear. We hypothesized that ventilation-induced neutrophil influx and MIP-2 production through activation of NF-kB/NRF pathway.Methods: Male C57BL/6 mice were exposed to low-tidal-volume (6 ml/kg) or high-tidal-volume (30 ml/kg) mechanical ventilation using room air with or without 2 mg/kg NF-kB inhibitor SN50 or 6 mg/kg NRF short interfering RNA (siRNA) or 100 mg/kg neutrophil elastase inhibitor administration. Nonventilated mice were used as controls.Results: Neutrophil elastase inhibitor ameliorated high-tidal-volume ventilation-induced lung injury, neutrophil influx, production of MIP-2 and malondialdehyde, activation of NF-kB and NRF, and disruption of bronchial microstructure in wild type mice. Mechanical stretch-augmented ALI was also attenuated with pharmacological inhibition of NF-kB activity by SN50 and NRF expression by NRF siRNA.Conclusions: Our data suggest that high-tidal-volume mechanical ventilation induces lung injury, neutrophil influx, oxidative stress, and production of MIP-2, at least partly, through activation of NF-kB/NRF pathway.Sources of Support: NSC 101-2314-B-182A-088-MY3.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/42/Suppl_57/P656}, eprint = {https://erj.ersjournals.com/content/42/Suppl_57/P656.full.pdf}, journal = {European Respiratory Journal} }