[en] BACKGROUND: Asthma is classified according to severity and inflammatory phenotype and is likely to be distinguished by specific microRNA (miRNA) expression profiles. OBJECTIVE: We sought to associate miRNA expression in sputum supernatants with the inflammatory cell profile and disease severity in asthmatic patients. METHODS: We investigated miRNA expression in sputum supernatants of 10 healthy subjects, 17 patients with mild-to-moderate asthma, and 9 patients with severe asthma using high-throughput, stem-loop, reverse transcriptase quantitative real-time PCR miRNA expression profiling (screening cohort, n = 36). Differentially expressed miRNAs were validated in an independent cohort (n = 60; 10 healthy subjects and 50 asthmatic patients). Cellular miRNA origin was examined by using in situ hybridization and reverse transcriptase quantitative real-time PCR. The functional role of miRNAs was assessed by using in silico analysis and in vitro transfecting miRNA mimics in human bronchial epithelial cells. RESULTS: In 2 independent cohorts expression of miR-629-3p, miR-223-3p, and miR-142-3p was significantly upregulated in sputum of patients with severe asthma compared with that in healthy control subjects and was highest in patients with neutrophilic asthma. Expression of the 3 miRNAs was associated with sputum neutrophilia, and miR-223-3p and miR-142-3p expression was associated also with airway obstruction (FEV1/forced vital capacity). Expression of miR-629-3p was localized in the bronchial epithelium, whereas miR-223-3p and miR-142-3p were expressed in neutrophils, monocytes, and macrophages. Transfecting human bronchial epithelial cells with miR-629-3p mimic induced epithelial IL-8 mRNA and protein expression. IL-1beta and IL-8 protein levels were significantly increased in sputum of patients with severe asthma and were positively associated with sputum neutrophilia. CONCLUSIONS: Expression of miR-223-3p, miR-142-3p, and miR-629-3p is increased in sputum of patients with severe asthma and is linked to neutrophilic airway inflammation, suggesting that these miRNAs contribute to this asthma inflammatory phenotype.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Maes, Tania; Universitair Ziekenhuis Gent - UZ > Department of Respiratory Medicine
Cobos, Francisco Avila; Universiteit Gent - Ugent > Center for Medical Genetics
SCHLEICH, FLorence ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie
Sorbello, Valentina; University of Torino > Department of Clinical and Biological Sciences
HENKET, Monique ; Centre Hospitalier Universitaire de Liège - CHU > Service de pneumologie - allergologie
De Preter, Katleen; Universiteit Gent - Ugent > Center for Medical Genetics
Bracke, Ken R.; Universitair Ziekenhuis Gent - UZ > Department of Respiratory Medicine
Conickx, Griet; Universitair Ziekenhuis Gent - UZ > Department of Respiratory Medicine
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