NF-kappa B blockade reduces the O-2-evoked rise in Na+ conductance in fetal alveolar cells

Electrophoretic mobility shift assays revealed minimal levels of NF-kappaB activity in rat distal lung epithelial cells cultured at fetal (23 mmHg) or adult alveolar (100 mmHg) P-O2, but revealed significant activation of thi s transcription factor in cells exposed to a rise in P-O2 mimicking that ex perienced at birth. This response was entirely abolished by pretreating cel ls with 5 mM sulfasalazine (SSA). This shift in P-O2 also evoked a rise in apical Na+ conductance (G(Na+)) that may underlie the O-2-evoked stimulatio n of Na+ transport seen in these cells. Pretreatment with SSA had no effect upon G(Na+) in cells cultured continually at adult or fetal P-O2 but did i nhibit the increase in G(Na+) Seen in cells that had experienced the rise i n P-O2. O-2-evoked activation of NF-kappaB may thus mediate the increased N a+ transport that occurs when the distal lung epithelial cells are exposed to a physiologically-relevant increase in PO2. (C) 2001 Academic Press.