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Asthma inflammatory phenotypes show differential microRNA expression in sputum

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Abstract
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.
Keywords
MIRNA EXPRESSION, CELLS, NLRP3 INFLAMMASOME, AIRWAY EPITHELIUM, GENE-EXPRESSION, EPITHELIAL-MESENCHYMAL TRANSITION, neutrophilic inflammation, sputum, microRNA, Asthma, MIR-223, PROLIFERATION, CANCER, INDUCTION

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MLA
Maes, Tania et al. “Asthma Inflammatory Phenotypes Show Differential microRNA Expression in Sputum.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 137.5 (2016): 1433–1446. Print.
APA
Maes, T., Avila Cobos, F., Schleich, F., Sorbello, V., Henket, M., De Preter, K., Bracke, K., et al. (2016). Asthma inflammatory phenotypes show differential microRNA expression in sputum. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 137(5), 1433–1446.
Chicago author-date
Maes, Tania, Francisco Avila Cobos, Florence Schleich, Valentina Sorbello, Monique Henket, Katleen De Preter, Ken Bracke, et al. 2016. “Asthma Inflammatory Phenotypes Show Differential microRNA Expression in Sputum.” Journal of Allergy and Clinical Immunology 137 (5): 1433–1446.
Chicago author-date (all authors)
Maes, Tania, Francisco Avila Cobos, Florence Schleich, Valentina Sorbello, Monique Henket, Katleen De Preter, Ken Bracke, Griet Conickx, Claire Mesnil, Jo Vandesompele, Lies Lahousse, Fabrice Bureau, Pieter Mestdagh, Guy Joos, Fabio LM Ricciardolo, Guy Brusselle, and Renaud Louis. 2016. “Asthma Inflammatory Phenotypes Show Differential microRNA Expression in Sputum.” Journal of Allergy and Clinical Immunology 137 (5): 1433–1446.
Vancouver
1.
Maes T, Avila Cobos F, Schleich F, Sorbello V, Henket M, De Preter K, et al. Asthma inflammatory phenotypes show differential microRNA expression in sputum. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2016;137(5):1433–46.
IEEE
[1]
T. Maes et al., “Asthma inflammatory phenotypes show differential microRNA expression in sputum,” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 137, no. 5, pp. 1433–1446, 2016.
@article{8067944,
  abstract     = {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.},
  author       = {Maes, Tania and Avila Cobos, Francisco and Schleich, Florence and Sorbello, Valentina and Henket, Monique and De Preter, Katleen and Bracke, Ken and Conickx, Griet and Mesnil, Claire and Vandesompele, Jo and Lahousse, Lies and Bureau, Fabrice and Mestdagh, Pieter and Joos, Guy and Ricciardolo, Fabio LM and Brusselle, Guy and Louis, Renaud},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  keywords     = {MIRNA EXPRESSION,CELLS,NLRP3 INFLAMMASOME,AIRWAY EPITHELIUM,GENE-EXPRESSION,EPITHELIAL-MESENCHYMAL TRANSITION,neutrophilic inflammation,sputum,microRNA,Asthma,MIR-223,PROLIFERATION,CANCER,INDUCTION},
  language     = {eng},
  number       = {5},
  pages        = {1433--1446},
  title        = {Asthma inflammatory phenotypes show differential microRNA expression in sputum},
  url          = {http://dx.doi.org/10.1016/j.jaci.2016.02.018},
  volume       = {137},
  year         = {2016},
}

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