Extracellular pH and lung infections

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During the past three decades most of the efforts to explain the cystic fibrosis (CF) phenotype explored non-genomic effects. At the beginning of the 90s we thought that the complex CF phenotype, including the susceptibility to infections, could not be explained only by non-genomics effects. Using differential display (at that time microarrays were not yet commercially available) que found a series of CFTR-dependent genes. c-Src was the first characterized and it was overexpressed, driving the overexpression of MUC1. Since most mucins are under c-Src control, this could explain the overexpression of mucins in cystic fibrosis and related diseases. In the same way, we believe that the high susceptibility to infections rely on the differential expression of CFTR-dependent genes. We have recently demonstrated that the second messenger for CFTR is Cl- and the existence of Cl- -dependent genes. Noteworthy, one of them resulted to be IL-1b, which form a vicious positive feedback loop that reinforce its own signal. The loop is initiated by increased Cl- accumulation. This has enormous implications for inflammatory diseases.This also includes possible changes in the extracellular pH, which are discussed in this review.

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