In vivo transfection of nuclear factor κB decoy protects pulmonary function against acute lung contusion in rabbits.

Abstract

The transcription factor nuclear factor κB (NF-κB) regulates the expression of numerous proinflammatory factors that may exacerbate the response to acute injury. We investigated the effect of an inhibitory NF-κB decoy oligodeoxynucleotide on proinflammatory factor expression and pulmonary function after acute lung contusion in rabbits. Thirty-minutes after acute lung contusion, the NF-κB decoy or a scrambled control oligodeoxynucleotide was injected via the jugular vein. Blood samples were collected for blood gas analysis and plasma tumor necrosis factor α, interleukin 1β (IL-1β), IL-13, and IL-10 were measured by enzyme-linked immunosorbent assay at 1, 2, 3, and 4 hours after contusion. In addition, NF-κB protein expression in lung tissue was detected by Western blot analysis. The blood PO2 decreased immediately after lung contusion, whereas PAO2 increased significantly, indicative of disrupted respiratory function. Respiratory function improved after sense NF-κB decoy injection but not after injection of the inactive scrambled form. Injection of NF-κB decoy resulted in significant inhibition of NF-κB protein expression in lung tissue and a reduction in the serum concentrations of proinflammatory cytokines tumor necrosis factor α and IL-1β compared with those of control rabbits injected with the scrambled decoy. In contrast, serum levels of the anti-inflammatory cytokines IL-10 and IL-13 increased after decoy injection compared with those of control animals and rabbits injected with the scrambled decoy. The sense NF-κB decoy protected respiratory function and reduced serum proinflammatory factor secretion after acute lung contusion. Inhibition of NF-κB may allow for preservation of pulmonary function for patients with acute lung injury.