The basic defect in cystic fibrosis (CF) is the loss of function of the CFTR protein, which causes dehydration of the airway surface. This condition favours bacterial infections. Despite the efficacy of modulators of CFTR (correctors and enhancers), many patients treated with these drugs show the persistence of bacterial infections, thus representing a continuous stimulus of inflammation. This situation is even more pronounced in people with CF who carry mutations that are not rescued by correctors and potentiators.

In this project, bronchial epithelial cells from people with CF and control subjects (without CF) were used, from which epithelia with characteristics similar to those of the in vivo tissue were generated in vitro, with the dual aim of studying the mechanisms by which inflammation alters epithelial processes and identifying cellular targets useful for pharmacological treatment.

After treatment with stimuli mimicking inflammation in vivo, the epithelia were studied by various methods to assess gene expression, the activity of CFTR and other proteins involved in the transport of chloride and other ions, and the degree of humidification, viscosity and acidity of the epithelial surface. The hypothesis that guided the experiments was that inflammation has negative effects on the chemical and physical properties of the airway surface.  

The results obtained indicate that inflammation underlies a vicious circle that worsens the consequences of loss of CFTR function by generating a dehydrated and hyperviscous state in the airways of people with CF. 
This situation can be resolved by using drugs that act on alternative targets, for example by inhibiting the SLC26A4 transport protein.

It will be necessary to confirm the validity of SLC26A4 as a useful therapeutic target in CF and to proceed with the identification of appropriate pharmacological inhibitors.