Microbiota Imbalance Contributes to COPD Deterioration by Enhancing IL-17a Production via miR-122 and miR-30a

Abstract

The changes of microbiota in lungs could change interleukin-17a (IL-17a) expression by altering microRNAs (miRNAs) profile, thus contributing to the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we aimed to study molecular mechanisms’ underlying effect of microbiota imbalance on COPD deterioration. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to analyze expression of miRNAs and IL-17a mRNA. ELISA was used to evaluate abundance of IL-17a in plasma, peripheral blood monocyte, and sputum of COPD mice and patients. Luciferase assay was performed to explore underlying molecular mechanisms. The expression of miR-122, miR-30a, and miR-99b were remarkably decreased in COPD mice, while the expression of IL-17a was notably increased in plasma, peripheral blood monocytes, and lung tissues of COPD mice. The levels of Lactobacillus/Moraxella and IL-17a expression were significantly enhanced in sputum of exacerbated COPD patients, along with notably decreased expression of miR-122 and miR-30a. Luciferase assay confirmed that miR-122 and miR-30a played an inhibitory role in IL-17a expression. We identified miR-122 and miR-30a as differentially expressed miRNAs in sputum and plasma of COPD patients in exacerbation-month12 group. Furthermore, downregulated miR-122 and miR-30a expression associated with microbiota imbalance may contribute to COPD deterioration by enhancing IL-17a production.

Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

“…Importantly, we further observed a 5-fold decrease in the expression of miR-122-5p on comparing miRNA population from lung-derived exosomes from COPD patients versus healthy smokers. Our results are in accordance with previous literature (50-52). For instance, Zhu et al (2020) demonstrated the downregulation of miR-122-5p in the sputum and plasma of COPD patients and proved that it functions as a negative regulator of IL-17A production (50).…”

“…Our results are in accordance with previous literature (50-52). For instance, Zhu et al (2020) demonstrated the downregulation of miR-122-5p in the sputum and plasma of COPD patients and proved that it functions as a negative regulator of IL-17A production (50). It is pertinent to mention here that though we did not find any commonly altered miRNAs in the exosomes from BALF or lung tissues of COPD patients, we found links that associate miRNA-mediated modulation of IL17-signalling amongst the diseased individual.…”

Distinct Exosomal miRNA Profiles from BALF and Lung Tissue from COPD and IPF Patients

“…Our results are in accordance with previous literature (50)(51)(52). For instance, Zhu et al (2020) demonstrated the downregulation of miR-122-5p in the sputum and plasma of COPD patients and proved that it functions as a negative regulator of IL-17A production (50). It is pertinent to mention here that though we did not find any commonly altered miRNAs in the exosomes from BALF or lung tissues of COPD patients, we found links that associate miRNA-mediated modulation of IL17-signalling amongst the diseased individual.…”

“…Our results are in accordance with previous literature (50)(51)(52). For instance, Zhu et al (2020) demonstrated the downregulation of miR-122-5p in the sputum and plasma of COPD patients and proved that it functions as a negative regulator of IL-17A production (50).…”

Effect of Methylation Status of lncRNA-MALAT1 and MicroRNA-146a on Pulmonary Function and Expression Level of COX2 in Patients With Chronic Obstructive Pulmonary Disease

“…In the next step, hPASMCs and rPASMCs were co-transfected with the wild-type or mutant-type MALAT1 promoter in conjunction with miR-146a mimics or a negative control miRNA. At 24 h after the transfection was started, the luciferase activity in transfected cells was evaluated by using a dual luciferase reporter gene assay kit (Promega) on a TD-20/20 luminometer (Turner Biosystems, Sunnyvale, CA, United States) based on the general protocols provided by the manufacturers of both the reporter gene assay kit and the luminometer ( Zhou et al, 2020 ; Zhu et al, 2020 ).…”