Asthma inflammatory phenotypes show differential microRNA expression in sputum - 05/05/16
, Francisco Avila Cobos, MSc b, Florence Schleich, MD, PhD c, Valentina Sorbello, PhD d, Monique Henket, MLT c, Katleen De Preter, PhD b, Ken R. Bracke, PhD a, Griet Conickx, Pharm a, Claire Mesnil, PhD e, Jo Vandesompele, PhD b, Lies Lahousse, PhD a, Fabrice Bureau, PhD e, Pieter Mestdagh, PhD b, Guy F. Joos, MD, PhD a, Fabio L.M. Ricciardolo, MD, PhD d, Guy G. Brusselle, MD, PhD a, Renaud Louis, MD, PhD cAbstract |
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-1β 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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Asthma, microRNA, sputum, neutrophilic inflammation
Abbreviations used : ACQ, BMI, FVC, GINA, HBEC, ICS, IQR, MAPK, miRNA, NOD, qPCR, SSC, VIM
Plan
| Supported by the Belgian Interuniversity Attraction Poles Program (IUAP) P7/30, Concerted Research Action of Ghent University BOF14-GOA-027, Belgium; Spearhead Immunology, Ghent University Hospital, Belgium; FWO Flanders (G.0A99.13 and G.0319.11N); and the Maro Fund of the King Baudouin Foundation. |
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| Disclosure of potential conflict of interest: T. Maes has received grants from Belspo (Belgian Federal Government-Interuniversity Attraction Poles) and Ghent University Hospital (Concerted Research action and Spearhead Immunology); has received the GlaxoSmithKline Clinical Science Award; has received travel support from GlaxoSmithKline and Boehringer Ingelheim; and is a shareholder in Oryzon Genomics. J. Vandesompele is cofounder, CSO, and member of the board of directors of Biogazelle and receives stock/stock options from Biogazelle. L. Lahousse has received travel support from the European Respiratory Society, the American Thoracic Society, and BVP. G. F. Joos has received grants from the Belgian Federal Government, Belspo, Ghent University Hospital, Spearhead Immunology, the Maro Fund (King Baudouin Foundation), AstraZeneca, Chiesi, GlaxoSmithKline, and Novartis; has consultant arrangements with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mundipharma, and Novartis; has received payment for lectures from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, and Sandoz Pharma; and has received travel support from AstraZeneca and Novartis. F. L. M. Ricciardolo is a board member for Mundipharma; has consultant arrangements with Novartis, Chiesi, and AstraZeneca; has received grants from Boehringer Ingelheim; and has received payment for lectures from Novartis, Chiesi, and Mundipharma. G. G. Brusselle is a member of advisory boards for Astra Zeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis and has received payment for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Mundipharma, and Zambon. R. Louis has received grants from the Federal Office for Scientific Affairs (IAP P7/30), GlaxoSmithKline, Novartis, Chiesi, and AstraZeneca; is a board member for GlaxoSmithKline, AstraZeneca, Novartis, Mundipharma, and Pfizer; has received payment for lectures from Novartis and Pfizer; and has received travel support from Boehringer Ingelheim. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 5
P. 1433-1446 - mai 2016 Retour au numéro
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