Cigarette Smoke modulates microRNA expression in primary human alveolar macrophages.

<bold>Background:</bold> Cigarette smoke (CS) is a major driver of many respiratory diseases including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco promotes oxidative imbalance, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression. MicroRNAs (miRNAs) are small, non-coding, single-stranded RNA that influence several biological processes through mRNA cleavage or translational repression. <bold>Aim:</bold> To assess the effects of CS on miRNA expression in human primary AMs obtained from the bronchoalveolar lavage (BAL) of ever- or never-smoker subjects and patients with COPD or NSCLC. <bold>Methods:</bold> BAL specimens were collected from a prospective cohort of 33 sex-matched subjects and expression of has-miR-34a-5p, 106a-5p 16-5p, 17-5p, 223-5p, and 20a-5p was assessed by RT-PCR before and after in vitro CS exposure. In addition, bioinformatic prediction of miRNA target genes associated with inflammation was performed. <bold>Results:</bold> In vitro stimulation with 10% CS for 24h of AMs obtained from never-smokers results in two specific trends, leading to upregulation of hsa-miR-34a-5p and 106a-5p (p< 0.01, respectively), 17-5p and 16-5p (p< 0.001, respectively) and negative modulation of hsa-miR-223-5p and 20a-5p (p< 0.01, respectively). In contrast, in vitro CS exposure in AMs obtained from individuals chronically exposed in vivo to CS or with pre-existing lung conditions such as COPD or NSCLC variably affects miRNAs. <bold>Conclusion:</bold> This study identified miRNA signatures in AMs exposed to CS, indicating that CS is an important driver of epigenetic changes that contributes to the onset of various lung diseases