What is it about?
The CFTR impairment determines Cl- accumulation, which in turn induce the secretion of IL-1b by using an unknown mechanism. c-Src inhibition partially block the IL-1b autocrine loop.
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Why is it important?
c-Src was the first signal element identified in the CFTR pathway. This was done many years ago by using differential display. It was also found that c-Src constitutes a bridge between the CFTR failure and the hyperstimulation of MUC1. Here it was also found that c-Src is chronically stimulated in Cystic Fibrosis (CF) cells and that it is involved in the initiation and maintenance of the IL-1b autocrine loop, under sterile conditions (in the absence of any infection, which is called "sterile inflammation"). Therefore, an inflammatory state occurs in CF which in intrinsic to the CFTR failure, and independent of any subsequent infection, which will of course exacerbate this pro-inflammatory state.
Perspectives
There are still many elements in the CFTR signaling pathway that are unknown. One important issue is to understand the mechanism by which Cl- accumulation induced IL-1b secretion.
Dr Tomás A. Santa Coloma
Institute for Biomedical Research (BIOMED), CONICET, UCA
Read the Original
This page is a summary of: CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling, Archives of Biochemistry and Biophysics, February 2017, Elsevier,
DOI: 10.1016/j.abb.2017.01.003.
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