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

In our experiments, PAK did not induce apoptosis in NCI-H292 cells. However, these cells are not completely resistant to apoptosis since staurosporine was able to induce caspase-3 and PARP cleavage. Thus, although CHAC1 was induced by Pa, it was not sufficient to induce cell apoptosis. It is conceivable that the level of induction of CHAC1 may be too low to promote apoptosis. In contrast, high induction of CHAC1 using an overexpression plasmid led to induction of PARP cleavage, indicative of cell apoptosis. Apoptosis dysfunction is still highly controversial in CF (44) , and our results are partly consistent with some previous studies. Indeed, even if Pa has been previously shown to induce apoptosis in lung epithelial cells, variable susceptibility between lung epithelial cells has been observed. Moreover, the PAO1 strain of Pa has been shown to induce apoptosis in human tracheal 9HTEo cells but not in primary nasal epithelial cells from polyps or in 16HBE14o bronchial cells, which are both resistant (45) . In contrast, other bronchial cell lines are permissive to apoptosis induced by Pa, such as IB3-1 (F508del/W1282X), C38, S9 (both IB3-1 corrected cells), CFT1-LCFSN, and CFT1-LC3 (F508del) cells. More recently, using Calu-3 polarized lung epithelial cells, researchers showed that PAO1 was able to induce apoptosis markers, such as active caspase-3, within 6-8 h. Additionally, the effects of the CFTR genotype on apoptosis of lung epithelial cells at baseline (44) or after Pa infection are still debated and may be dependent on which specific marker of apoptosis is being evaluated (45, 46) .