miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD
| Autor: | Laura Florez-Sampedro, Hataitip Tasena, Irene H. Heijink, Wim Timens, Tillie L. Hackett, Jacobien A. Noordhoek, Alen Faiz, Dirkje S. Postma, Corry-Anke Brandsma, Emmanuel T. Osei |
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| Přispěvatelé: | Groningen Research Institute for Asthma and COPD (GRIAC), Chemical and Pharmaceutical Biology, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Respiratory System Inflammation Bronchi Polymorphism Single Nucleotide Epithelium Cigarette Smoking 03 medical and health sciences Pulmonary Disease Chronic Obstructive 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Interleukin-1alpha medicine Journal Article Humans Fibroblast Alleles COPD Lung business.industry Interleukin-8 Interleukin Epithelial Cells Tobacco Products Fibroblasts medicine.disease Antibodies Neutralizing Coculture Techniques MicroRNAs 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Cell culture Culture Media Conditioned Immunology medicine.symptom Signal transduction business Signal Transduction |
| Zdroj: | European Respiratory Journal, 49(5). EUROPEAN RESPIRATORY SOC JOURNALS LTD |
| ISSN: | 0903-1936 |
| Popis: | We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived inflammation in the lung epithelial–mesenchymal trophic unit. Since miR-146a-5p has been shown to negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1α-driven inflammation in chronic obstructive pulmonary disease (COPD).Human bronchial epithelial (16HBE14o-) cells were co-cultured with control and COPD-derived primary human lung fibroblasts (PHLFs), and miR-146a-5p expression was assessed with and without IL-1α neutralising antibody. Genomic DNA was assessed for the presence of the single nucleotide polymorphism (SNP) rs2910164. miR-146a-5p mimics were used for overexpression studies to assess IL-1α-induced signalling and IL-8 production by PHLFs.Co-culture of PHLFs with airway epithelial cells significantly increased the expression of miR-146a-5p and this induction was dependent on epithelial-derived IL-1α. miR-146a-5p overexpression decreased IL-1α-induced IL-8 secretion in PHLFs via downregulation of IL-1 receptor-associated kinase-1. In COPD PHLFs, the induction of miR-146a-5p was significantly less compared with controls and was associated with the SNP rs2910164 (GG allele) in the miR-146a-5p gene.Our results suggest that induction of miR-146a-5p is involved in epithelial–fibroblast communication in the lungs and negatively regulates epithelial-derived IL-1α induction of IL-8 by fibroblasts. The decreased levels of miR-146a-5p in COPD fibroblasts may induce a more pro-inflammatory phenotype, contributing to chronic inflammation in COPD. |
| Databáze: | OpenAIRE |
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