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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.

SUBMITTER: Zhu K

PROVIDER: S-EPMC7558803 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Zhu Ke K Zhou Sijing S Xu Aiqun A Sun Li L Li Min M Jiang Huihui H Zhang Binbin B Zeng Daxiong D Fei Guanghe G Wang Ran R

Molecular therapy. Nucleic acids 20200923

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 ...[more]

PMID: 33230454

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Project description:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a heterogeneous smoking-related disease characterized by airway obstruction and inflammation. This inflammation may persist even after smoking cessation and responds variably to corticosteroids. Personalizing treatment to biologically similar "molecular phenotypes" may improve therapeutic efficacy in COPD. IL-17A is involved in neutrophilic inflammation and corticosteroid resistance, and thus may be particularly important in a COPD molecular phenotype. METHODS:We generated a gene expression signature of IL-17A response in bronchial airway epithelial brushings from smokers with and without COPD (n = 238), and validated it using data from 2 randomized trials of IL-17 blockade in psoriasis. This IL-17 signature was related to clinical and pathologic characteristics in 2 additional human studies of COPD: (a) SPIROMICS (n = 47), which included former and current smokers with COPD, and (b) GLUCOLD (n = 79), in which COPD participants were randomized to placebo or corticosteroids. RESULTS:The IL-17 signature was associated with an inflammatory profile characteristic of an IL-17 response, including increased airway neutrophils and macrophages. In SPIROMICS the signature was associated with increased airway obstruction and functional small airways disease on quantitative chest CT. In GLUCOLD the signature was associated with decreased response to corticosteroids, irrespective of airway eosinophilic or type 2 inflammation. CONCLUSION:These data suggest that a gene signature of IL-17 airway epithelial response distinguishes a biologically, radiographically, and clinically distinct COPD subgroup that may benefit from personalized therapy. TRIAL REGISTRATION:ClinicalTrials.gov NCT01969344. FUNDING:Primary support from the NIH, grants K23HL123778, K12HL11999, U19AI077439, DK072517, U01HL137880, K24HL137013 and R01HL121774 and contracts HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C and HHSN268200900020C.

Dataset Information

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

Publications

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

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