Pulmonary overexpression of inhibitor κBα decreases the severity of ventilator-induced lung injury in a rat model M. Hayes, G.F. Curley, C. Masterson,

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Pulmonary overexpression of inhibitor κBα decreases the severity of ventilator-induced lung injury in a rat model M. Hayes, G.F. Curley, C. Masterson, M. Contreras, B. Ansari, J. Devaney, D. O'Toole, J.G. Laffey British Journal of Anaesthesia Volume 113, Issue 6, Pages 1046-1054 (December 2014) DOI: 10.1093/bja/aeu225 Copyright © 2014 The Author(s) Terms and Conditions

Fig 1 Overexpression of IκBα reduced NF-κB activity. Delivery of the AAV encoding IκBα resulted in a dose-dependent increase in lung homogenate IκBα FLAG mRNA expression (a) and IκBα protein concentrations, as demonstrated by the representative western blot (b), and by measurement of IκBα in lung homogenates from all animals in each group by ELISA (c). IκBα decreased VILI-induced nuclear accumulation of the activated P65 subunit of NF-κB (d).Vehicle, animals that received intratracheal vehicle alone; IκBα 1×1010, animals that received 1×1010 AAV6 particles encoding IκBα; IκBα 5×1010, animals that received 5×1010 AAV6 particles encoding IκBα; Null, animals that received 1×1010 AAV6 particles encoding a null transgene. ELISA, enzyme-linked immunosorbent assay. *Significantly different from the vehicle group (P<0.05, anova). British Journal of Anaesthesia 2014 113, 1046-1054DOI: (10.1093/bja/aeu225) Copyright © 2014 The Author(s) Terms and Conditions

Fig 2 IκBα decreased the severity of VILI. Overexpression of IκBα attenuated the decrement in arterial oxygenation (a), and static lung compliance (b) after VILI, and decreased BAL protein concentrations (c), after VILI. Overexpression of IκBα attenuated BAL neutrophil infiltration (d). Abbreviations in Figure 1. *Significantly different from the vehicle group (P<0.05, anova). British Journal of Anaesthesia 2014 113, 1046-1054DOI: (10.1093/bja/aeu225) Copyright © 2014 The Author(s) Terms and Conditions

Fig 3 IκBα decreased structural lung injury induced by VILI. Overexpression of IκBα attenuated the decrement in alveolar airspace and the increase in alveolar tissue (a) after VILI. (b)–(e) demonstrate images from a ventilator injured lung that received intratracheal vehicle (b), 1×1010 IκBα (c), 5×1010 IκBα, (d) or null vector (e). Abbreviations in Figure 1. *Significantly different from the vehicle group (P<0.05, anova). The scale bar equals 200 µm. British Journal of Anaesthesia 2014 113, 1046-1054DOI: (10.1093/bja/aeu225) Copyright © 2014 The Author(s) Terms and Conditions