Pneumologie 2016; 70 - P378
DOI: 10.1055/s-0036-1572294

Airway epithelial cells secrete altered exosomal microRNAs in murine experimental and human paediatric asthma

S Bartel 1, N Schulz 2, A Schamberger 3, F Alessandrini 4, E Noessner 5, SM Stick 6, A Kicic 6, O Eickelberg 3, RJ Freishtat 7, S Krauss-Etschmann 8
  • 1Leibniz-Center for Medicine and Biosciences, Research Center Borstel
  • 2Comprehensive Pneumology Center (Cpc-M), Institute of Lung Biology and Disease, Helmholtz Zentrum München and University Hospital of the Ludwig Maximilians University (Lmu), Member of the German Center for Lung Research (Dzl); Children's Hospital of the Ludwig Maximilians University, Munich
  • 3Comprehensive Pneumology Center (Cpc-M), Institute of Lung Biology and Disease, Helmholtz Zentrum München and University Hospital of the Ludwig Maximilians University (Lmu), Member of the German Center for Lung Research (Dzl), Munich
  • 4Center of Allergy and Environment (Zaum), Technische Universität and Helmholtz Zentrum München
  • 5Institute of Molecular Immunology, Helmholtz Zentrum München
  • 6Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia; School of Paediatrics and Child Health, The University of Western Australia
  • 7Division of Emergency Medicine, Children's National Medical Center, Washington DC
  • 8Leibniz-Center for Medicine and Biosciences, Research Center Borstel; Institute for Experimental Medicine, Christian-Albrechts-Universität zu Kiel

Background: miRNAs (miR) are critical regulators of the immune system. Recently they have been shown to be secreted into exosomes for inter-cell communication (Valadi et al., Nat Cell Biol, 2007). We previously identified an up-regulation of miR-17, -144 and -21 in murine lung homogenate in Ovalbumin (OVA) induced allergic airway inflammation (AAI) and in nasal epithelial cells of children with allergic asthma.

Objective: We now aimed to decipher the role of the bronchial epithelium in the production and secretion of miRNAs in asthma.

Methods: Primary normal human bronchial epithelial (NHBE) cells were cultured at the air-liquid interface and treated with Interleukin (IL)-13 to model a T-helper 2 environment. Exosomes were isolated by Exoquick-TC from cell culture, broncho-alveolar lavage fluid (BALF) of mice and human nasal washes and quantified by flow cytometry or ELISA for CD63. miRNA levels were assessed by qRT-PCR.

Results: Exosomal miR-17 and -21 levels were initially increased upon IL-13 treatment in the basal cell compartment and later on the apical. In murine BALF of OVA-induced AAI miR-17 and -21 were significantly up-regulated while exosome amounts were similar. These finding were consolidated in house dust mite induced AAI. All miRNAs could be detected in exosomes of human nasal washes.

Conclusion: miR-17 and -21 levels in exosomes were increased upon in vitro IL-13 treatment of primary NHBE cells and in biofluids of murine AAI and human paediatric asthma. A distribution of miRNAs via exosomes could perpetuate an asthmatic response and expand it to other cell types such as immune cells.