CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa

Perra, Léa; Balloy, Viviane; Foussignière, Tobias; Moissenet, Didier; Petat, Hortense; Mungrue, Imran N.; Touqui, Lhousseine; Corvol, Harriet; Chignard, Michel; Guillot, Loic

Because CHAC1 has been shown to be associated with the PERK pathway (11), we hypothesized that induction of CHAC1 by LPS from Pa may be mediated by PERK. Therefore, we used a PERK inhibitor and tunicamycin (TM) as a positive control for Figure 2E ). activation of the CHAC1 and PERK pathway (11) . As expected, compared with untreated NCI-H292 cells, LPS and TM induced CHAC1 mRNA expression. When cells were treated with TM and PERK inhibitor, there was a significant 90.3% decrease in CHAC1 mRNA expression compared with that in cells treated with TM alone (Figure 3A) . However, when cells were treated with LPS and PERK inhibitor, CHAC1 mRNA expression was not significantly different from that in cells treated with LPS only (Figure 3A) . We then hypothesized that this induction of CHAC1 by LPS would directly pass through ATF4. Indeed, we observed that LPS was able to activate ATF4 and that siRNA against ATF4 inhibited this induction ( Figure 3B) . The inhibition of ATF4 expression by the siRNA ATF4 (∼60%) was associated with an inhibition of CHAC1 induction by LPS (Figures 3C,D) .