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Proteases and CFTR : in vitro and in vivo regulation in lung epithelial cells and alveolar macrophages
Cystic fibrosis (CF) is the most common genetically inherited disease in Caucasians (1 in 2500 newborns) and is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR). The most prevalent CFTR mutation dF508 (which constitutes 70% of all mutations) results in an incorrect targeting of the CFTR molecule to the membrane.
We have shown that NE has a deleterious effect on CFTR structure and channel function in epithelial cells in vitro and in vivo in a P.a lung infection model (Le Gars et al, AJRCCM, 2013). Interestingly, we showed that NE inactivate CFTR through an intracellular calpain activation pathway, but the potential inflammatory exacerbative effect of proteases (NE and others ) on dF508 in vivo remains to be studied. Importantly, we have shown that other factors than NE may also be important in inducing the degradation of CFTR in the P.a infection model, and among these, we determined in preliminary results that Las B, a zinc metallo-exoprotease secreted by P.a type 2 secretion system can also degrade CFTR in vitro.
We wish here to consolidate these findings by testing in vitro whether NE can
|Project amount (€):||65.004|