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Since miR-146a-5p has been shown to\u00a0negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1\u03b1-driven inflammation in chronic obstructive pulmonary disease (COPD).<\/jats:p><jats:p>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-1\u03b1 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-1\u03b1-induced signalling and IL-8 production by PHLFs.<\/jats:p><jats:p>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-1\u03b1. miR-146a-5p overexpression decreased IL-1\u03b1-induced IL-8 secretion in PHLFs<jats:italic>via<\/jats:italic>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.<\/jats:p><jats:p>Our results suggest that induction of miR-146a-5p is involved in epithelial\u2013fibroblast communication in the lungs and negatively regulates epithelial-derived IL-1\u03b1 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.<\/jats:p>","DOI":"10.1183\/13993003.02538-2016","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:10:18Z","timestamp":1495757418000},"page":"1602538","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":51,"title":["miR-146a-5p plays an essential role in the aberrant epithelial\u2013fibroblast cross-talk in COPD"],"prefix":"10.1183","volume":"49","author":[{"given":"Emmanuel 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