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

The fine tuning of immune responses by the UPR has been extensively studied (37) . However, its contribution to the regulation of cytokine production in bacterial infection is not well understood (16) . Here, we observed that inhibition of CHAC1 mRNA expression by siRNA promoted IL-8 and CCL2 expression and PGE2 secretion, suggesting that CHAC1 prevents excessive inflammatory responses dependent on the NF-κB p65 pathway. These results were consistent with a recent study reporting that bronchial epithelial cells undergoing ER stress showed reduced IL-8 and CXCL1 production in the presence of inflammatory stimuli (38) . Indeed, pretreatment of bronchial epithelial cells with TM [shown here and by others (11) to be able to increase CHAC1 expression] can prevent IL-8 and CXCL1 production. In contrast, inhibition of CHAC1 mRNA expression by siRNA inhibits IL-6 production, suggesting that CHAC1 may promote IL-6 expression. Our results were consistent with a previous study showing that TM promotes IL-6 secretion in bronchial IB3-1 (CF deficient) and C38 cells stimulated with flagellin (12) . Previous works have demonstrated that IL-6 production in A375 skin cells is dependent on CHOP (39) . However, CHOP is expected to be upstream in the CHAC1 pathway and does not explain our results; future studies are needed to determine how the IL-6 pathway is affected specifically in lung epithelial cells.