Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa -: art. no. 2

Background: The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the alpha, beta and gamma subunits of the epithelial sodium channel (ENaC) and the catalytic subunit of Na+- K+-ATPase. Methods: Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c) and susceptible (DBA/2, C57BL/6 and A/J) mouse strains. The mRNA expression of ENaC and Na+- K+-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. Results: The infection of the different mouse strains evoked regulation of a and ENaC mRNA. Following Pseudomonas instillation, the expression of alpha ENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection ( p < 0.05). The relative expression of ENaC mRNA was transiently increased to a median of 241%, 24 h post- infection before decreasing to a median of 43% and 54% of control on days 3 and 7 post- infection ( p < 0.05). No significant modulation of gamma ENaC mRNA was detected although the general pattern of expression of the subunit was similar to alpha and beta subunits. No modulation of alpha Na-1(+)- K+-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. Conclusions: These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs.