Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa

Affiliation: André Dagenais: Centre hospitalier de l'Université de Montréal/ Hôtel-Dieu, Département de médecine, Université de Montréal. Yves Berthiaume: Médecine et spécialités médicales, Faculté de médecine

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 a, ß and ? 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 ß ENaC mRNA. Following Pseudomonas instillation, the expression of aENaC 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 ßENaC 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 ?ENaC mRNA was detected although the general pattern of expression of the subunit was similar to a and ß subunits. No modulation of a1Na+-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.