MiR-223-3p has a regulatory effect in airway inflammation in asthma and COPD
Cellular and molecular mechanisms (English)Changes in miR-223-3p expression have been associated with inflammation in obstructive lung disease. We aimed to confirm previous findings on miR-223-3p expression and its association with inflammatory cells in an independent asthma and COPD cohort. Additionally, we investigated the effect of miR-223-3p on pro-inflammatory activity of airway epithelial cells (AEC) using asthma and COPD-related triggers.
MiR-223-3p expression was assessed in bronchial biopsies of asthma patients and healthy controls and in lung tissue of COPD patients and non-COPD controls. Primary AEC from asthma, COPD patients and control donors were transfected with miR-223-3p mimic, treated with house dust mite, cigarette smoke extract or viral mimic poly-(I:C) and expression and secretion of GM-CSF and CXCL8 was measured.
Bronchial biopsies from asthmatics had significantly higher miR-223-3p levels compared to controls, with a positive correlation between miR-223-3p and eosinophils. Lung tissue of COPD patients had higher miR-223-3p levels compared to controls, with a positive correlation between miR-223-3p and neutrophils. In AEC, miR-223-3p was hardly detectable. Overexpression of miR-223-3p in control-derived AEC significantly reduced the expression and secretion GM-CSF and CXCL8 at baseline and upon stimulation, with a same trend for asthma-derived AEC. However, COPD-derived AEC were less sensitive to these regulatory effects.
Higher levels of miR-223-3p in asthma and COPD patients are associated with eosinophilia and neutrophilia. Our in vitro data suggest that miR-223-3p acts in a negative feedback loop to control pro-inflammatory airway epithelial activity. Ongoing studies are being performed to asses if this regulatory mechanism is disturbed in diseased epithelium.