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ENaC contributes to macrophage dysfunction in cystic fibrosis
Biorxiv : the Preprint Server for Biology
|November 22, 2024
Summary
Epithelial sodium channel (ENaC) is overexpressed in cystic fibrosis (CF) immune cells, impairing macrophage function. Inhibiting ENaC in CF macrophages may offer a new therapeutic strategy for infection and inflammation control.
Area of Science:
- Immunology
- Cell Biology
- Ion Channel Physiology
Background:
- Cystic fibrosis (CF) is a genetic disorder caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR).
- CFTR and epithelial sodium channel (ENaC) play roles in immune cell function, but ENaC's impact on CF immune responses is unclear.
- Understanding ion channel regulation of CF immune function may lead to new treatment approaches for chronic infections.
Purpose of the Study:
- To investigate the hypothesis that ENaC is aberrantly expressed in CF macrophages.
- To determine if ENaC directly contributes to impaired phagocytic and inflammatory functions in CF.
Main Methods:
- Characterized ENaC expression in human immune cells from CF and non-CF donors.
- Assessed monocyte-derived macrophage (MDM) function and bacterial killing with ENaC modulation.
Main Results:
- ENaC was overexpressed in CF MDMs, lymphocytes, and granulocytes at transcript and protein levels.
- ENaC inhibition with Amiloride normalized ROS production, improved autophagy, and decreased pro-inflammatory cytokines in CF MDMs.
- Amiloride treatment also increased CFTR expression and normalized sodium channel expression in CF MDMs.
Conclusions:
- ENaC is overexpressed in CF immune cells, correlating with abnormal macrophage function.
- ENaC modulation presents a potential therapeutic target for CF infection control, alone or with CFTR modulators.
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