Archivos de bronconeumologia · 2025
The Role of miR-320d in Regulation of Cigarette Smoke-Induced Pro-Inflammatory Responses in COPD.
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Roffel Mirjam P, Brandsma Corry-Anke, Faiz Alen, Jonker Marnix R, Timens Wim, Joos Guy F, Brusselle Guy G, Maes Tania, Bracke Ken R, van den Berge Maarten, Heijink Irene H
Аннотация
INTRODUCTION: The mechanisms driving abnormal pro-inflammatory responses to cigarette smoke in COPD remain unclear. MicroRNA (miR)-320d was previously shown to have anti-inflammatory effects, being upregulated by inhaled corticosteroids. Therefore, our objective was to study whether miR-320d suppresses smoke-induced airway epithelial pro-inflammatory responses and if this is compromised in COPD.
METHODS: We investigated the anti-inflammatory mechanisms of miR-320d in cigarette smoke extract (CSE)-exposed primary bronchial epithelial cells (PBECs), comparing COPD and control cells using a miR-320d mimic. Additionally, we assessed whether miR-320d expression is altered with COPD and its severity, investigating lung tissue from two independent cohorts of non-COPD controls (non/current/ex-smokers) and COPD patients (current/ex-smokers) with mild/moderate and severe disease.
RESULTS: MiR-320d overexpression attenuated baseline and CSE-induced pro-inflammatory CXCL8, IL-1α and GM-CSF secretion in non-COPD-derived PBECs. This effect was not observed for CXCL8 and IL-1α in COPD-derived PBECs. RNA-sequencing showed that miR-320d significantly regulates the expression of 137 genes in CSE-exposed epithelium, the upregulated genes being enriched in "interleukin-33-mediated signaling" and the downregulated genes in "response to cytokine" (including IRAK1) pathways. Higher miR-320d levels were associated with lower IRAK1 expression in control but not COPD-derived PBECs. Finally, miR-320d levels were lower in lung tissue of COPD patients vs non-smoking controls and in severe vs mild/moderate COPD patients.
CONCLUSIONS: miR-320d's suppressive effect on bronchial epithelial pro-inflammatory responses cells may be compromised in COPD. Additionally, miR-320d expression in lung tissue was lower with COPD severity. Thus, lower miR-320d anti-inflammatory action may contribute to persisting inflammation in COPD.
METHODS: We investigated the anti-inflammatory mechanisms of miR-320d in cigarette smoke extract (CSE)-exposed primary bronchial epithelial cells (PBECs), comparing COPD and control cells using a miR-320d mimic. Additionally, we assessed whether miR-320d expression is altered with COPD and its severity, investigating lung tissue from two independent cohorts of non-COPD controls (non/current/ex-smokers) and COPD patients (current/ex-smokers) with mild/moderate and severe disease.
RESULTS: MiR-320d overexpression attenuated baseline and CSE-induced pro-inflammatory CXCL8, IL-1α and GM-CSF secretion in non-COPD-derived PBECs. This effect was not observed for CXCL8 and IL-1α in COPD-derived PBECs. RNA-sequencing showed that miR-320d significantly regulates the expression of 137 genes in CSE-exposed epithelium, the upregulated genes being enriched in "interleukin-33-mediated signaling" and the downregulated genes in "response to cytokine" (including IRAK1) pathways. Higher miR-320d levels were associated with lower IRAK1 expression in control but not COPD-derived PBECs. Finally, miR-320d levels were lower in lung tissue of COPD patients vs non-smoking controls and in severe vs mild/moderate COPD patients.
CONCLUSIONS: miR-320d's suppressive effect on bronchial epithelial pro-inflammatory responses cells may be compromised in COPD. Additionally, miR-320d expression in lung tissue was lower with COPD severity. Thus, lower miR-320d anti-inflammatory action may contribute to persisting inflammation in COPD.