Asthma inflammatory phenotypes show differential microRNA expression in sputum

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:137

Article

Maes, Tania¹  Cobos, Francisco Avila²  Schleich, Florence³  Sorbello, Valentina⁴  Henket, Monique³  De Preter, Katleen²  Bracke, Ken R.¹  Conickx, Griet¹  Mesnil, Claire^5,6  Vandesompele, Jo²  Lahousse, Lies¹  Bureau, Fabrice^5,6  Mestdagh, Pieter²  Joos, Guy F.¹  Ricciardolo, Fabio L. M.⁴  Brusselle, Guy G.¹  Louis, Renaud³ 

[1] Ghent Univ Hosp, Dept Resp Med, Blok B,Room 420,De Pintelaan 185, B-9000 Ghent, Belgium

[2] Univ Ghent, Ctr Med Genet, Liege, Belgium

[3] CHU Sart TilmanB35, Dept Resp Med, Liege, Belgium

[4] Univ Turin, Dept Clin & Biol Sci, I-10124 Turin, Italy

[5] Univ Liege, GIGA Res Ctr, Dept Cellular & Mol Immunol, B-4000 Liege, Belgium

[6] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium

关键词: Asthma;    microRNA;    sputum;    neutrophilic inflammation;   

DOI  :  10.1016/j.jaci.2016.02.018

来源: Elsevier

【 摘 要 】

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-1 beta 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.

【 授权许可】

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