Author: Perra, Léa; Balloy, Viviane; Foussignière, Tobias; Moissenet, Didier; Petat, Hortense; Mungrue, Imran N.; Touqui, Lhousseine; Corvol, Harriet; Chignard, Michel; Guillot, Loic
Title: CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa Document date: 2018_11_29
ID: 10fe70kl_39
Snippet: We confirmed our previous transcriptomic data showing that CHAC1 mRNA was overexpressed in primary non-CF epithelial cells compared with its expression in CF cells at baseline and upon Pa infection. Additionally, Pa and two of its virulence factors, LPS and flagellin, the respective ligands of Toll-Like Receptor (TLR) 4 and TLR5, were able to induce CHAC1 at the transcriptional level in bronchial epithelial NCI-H292 cells. As previously shown in .....
Document: We confirmed our previous transcriptomic data showing that CHAC1 mRNA was overexpressed in primary non-CF epithelial cells compared with its expression in CF cells at baseline and upon Pa infection. Additionally, Pa and two of its virulence factors, LPS and flagellin, the respective ligands of Toll-Like Receptor (TLR) 4 and TLR5, were able to induce CHAC1 at the transcriptional level in bronchial epithelial NCI-H292 cells. As previously shown in Neuro2a (23) or HEK cells (26) , we were able to detect CHAC1 protein expression only after MG-132 treatment, suggesting the involvement of the proteasome pathway in the stability of the protein (26) . This induction of CHAC1 mRNA expression was observed not only with the laboratory strain PAK but also with freshly isolated clinical strains. Interestingly, S. maltophilia and S. aureus, both known to chronically infect CF patients, were not able to induce CHAC1 mRNA expression to similar levels. Using cellular infection models, other transcriptomic studies have consistently shown CHAC1 upregulation with microorganisms, including human coronavirus (27) , human cytomegalovirus (28), tick-borne flaviviruses (29) , Zika virus (30) , and the bacterium Mycoplasma hominis (31) . In these studies, the specific role of CHAC1 was not investigated. However, CHAC1 is essential as embryonic lethality was observed in mice with deletion of the Chac1 gene (32) .
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