What is it about?
Cells derived from cystic fibrosis patients or cells with impaired CFTR function accumulates Cl- which in turn induce the secretion of interleukin-1beta (IL1B). This in turn reduces the mitochondrial respiratory Complex I activity and induces increased ROS levels (in cytoplasm and mitochondria). Disruption of the IL1B signaling rescues the Complex I activity and improves ROS levels.
Featured Image
Why is it important?
The results suggest that in cystic fibrosis exists a basal, sterile, inflammation, initiated by IL1B, which produce a reduction in the respiratory chain efficiency and an increased oxidative stress. The mitochondrial defect can be restored to normal values by using the IL1B antagonist anakinra or by using blocking antibodies. This sterile inflammation might be exacerbated after infections are installed, although the basal inflammatory state seems to be present due to the excess of Cl-, which regulates the IL-1b secretion, as it was later demonstrated.
Perspectives
This add further evidences for the presence of an intrinsic proinflammatory state in CF cells, even in the absence of infections. The secreted IL1B produces an autocrine positive feedback loop that enhances its own expression, eventually affecting the mitochondrial activity and creating an oxidative stress condition. It would be important to determine the mechanisms by which the increased intracellular Cl- induces an enhanced IL1B secretion and proinflammatory state.
Dr Tomás A. Santa Coloma
Institute for Biomedical Research (BIOMED), CONICET, UCA
Read the Original
This page is a summary of: Disruption of Interleukin-1β Autocrine Signaling Rescues Complex I Activity and Improves ROS Levels in Immortalized Epithelial Cells with Impaired Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Function, PLoS ONE, June 2014, PLOS,
DOI: 10.1371/journal.pone.0099257.
You can read the full text:
Contributors
The following have contributed to this page
