NF-κB Blockade Reduces the O2-Evoked Rise in Na+ Conductance in Fetal Alveolar Cells

Electrophoretic mobility shift assays revealed minimal levels of NF-κB activity in rat distal lung epithelial cells cultured at fetal (23 mmHg) or adult alveolar (100 mmHg) PO2, but revealed significant activation of this transcription factor in cells exposed to a rise in PO2 mimicking that experienced at birth. This response was entirely abolished by pretreating cells with 5 mM sulfasalazine (SSA). This shift in PO2 also evoked a rise in apical Na+ conductance (GNa+) that may underlie the O2-evoked stimulation of Na+ transport seen in these cells. Pretreatment with SSA had no effect upon GNa+ in cells cultured continually at adult or fetal PO2 but did inhibit the increase in GNa+ seen in cells that had experienced the rise in PO2. O2-evoked activation of NF-κB may thus mediate the increased Na+ transport that occurs when the distal lung epithelial cells are exposed to a physiologically-relevant increase in PO2.