An investigation has discovered that having less microRNA, specifically less miR-146a-5p, could make the immune system unable to control the inflammation that occurs in infants and children who are infected with bronchiolitis or wheezing –noises in breathing– , so it would thus promote the chronification of these health problems in some children who suffer from them.
This great discovery has been made by members of the CIBER for Respiratory Diseases (CIBERES) and the Jiménez Díaz Foundation Health Research Institute (IIS-FJD), and thanks to the collaboration of researchers from the CIBER for Infectious Diseases (CIBERINFEC) belonging to the Severo Hospital Ochoa, the Hospital de la Paz, the Alfonso X el Sabio University and the National Center for Microbiology (ISCIII).
Having bronchiolitis or wheezing during childhood causes a deregulation in the immune response and increases the risk of it becoming a chronic problem, which can end up leading to diseases such as asthma. For this reason, the researchers wanted to know why they could lengthen so much over time and found that they were due to epigenetic modifications.
Among those pointed out by the authors are the regulation of gene transcription at the level of microRNAs, small RNA molecules that condition the expression of genes in human tissues. The tests carried out consisted of molecular and cell biology techniques that were based on nasopharyngeal aspirates from infants with bronchiolitis during the disease and after having overcome it, from children with episodes of wheezing and a healthy control group. Tests were also done in in vitro models of small airway epithelial cells from healthy children.
Reduction in miR-146a-5p expression in the airways
The results, which have been published in the journal Cells, pointed to miR-146a-5p as the biomarker responsible for the immune deregulation and loss of control of the inflammatory response found in children with bronchiolitis and wheezing analyzed in the study.
“A reduction in miR-146a-5p expression was observed in the airways of infants with bronchiolitis and in samples from infants who suffered from wheezing episodes, compared to controls. In the children who overcame bronchiolitis, the presence of miR-146a-5p was increased, although without reaching the levels of healthy controls, and could be key in the chronicity of the inflammation”, explained Victoria del Pozo, one of the researchers.
The miR-146a-5p biomarker is responsible for immune deregulation and loss of control of the inflammatory response in children with bronchiolitis and wheezing
In addition, nasopharyngeal aspirate tests also found that a lower appearance of this microRNA was associated with increased expression of the PTGS2 gene, a molecule associated with the immune system, and with TSLP, which is linked to infections in the epithelial cells of the lungs .
When they stimulated small airway epithelial cells from healthy participants with a viral analog, they saw an increase in miR-146a-5p. “These results observed in vitro using cells from healthy individuals, added to the results of the analysis of miR-146a-5p in the airways of children with bronchiolitis and wheezing episodes compared to healthy children, indicate that, under normal conditions, viral infections should to increase the expression of miR-146a-5p as a control mechanism of the inflammatory defense reactions themselves”, explains José Manuel Rodrigo.
However, this reduction in microRNA, which has anti-inflammatory capabilities, could make the immune system unable to restore inflammation to normal levels.
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