The estrogen-induced miR-19 downregulates secretory leucoprotease inhibitor expression in monocytes
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Compared to females, males are more susceptible to acute viral and other respiratory tract infections that display greater severity and higher mortality. In contrast, females tend to fare worse with chronic inflammatory diseases. Circulating 17β-estradiol (E2) is a female-specific factor that may influence the progression of human lung diseases. Here we hypothesize that E2 modulates the inflammatory response of monocytes through microRNA (miRNA)-based modulation of secretory leucoprotease inhibitor (SLPI), an antiprotease with immunomodulatory effects. Monocytic cells were treated ± E2, and differentially expressed miRNAs were identified using PCR profiling. Cells were transfected with miRNA mimics or antimiRs and SLPI mRNA and protein levels were quantified. Luciferase activity assay using wildtype and ΔmiR-19a/b-SLPI3'UTR reporter constructs and chromatin immunoprecipitation on E2-treated monocytes were performed. E2 downregulated SLPI and upregulated miR-19 expression in monocytes. Transfection with premiR-19b reduced SLPI mRNA and protein levels and this effect was abrogated using antimiRs against miR-19b. miR-19b directly binds the SLPI 3'UTR. The mechanism responsible for E2-mediated upregulation of miR-19 occurs via increased MIR17HG promoter activity mediated by c-MYC. Overall E2 decreases SLPI expression in human monocytic cells, via changes in miRNA expression and highlights the potential for estrogen to modulate the innate immune system.
Date Issued
2020-01
Date Acceptance
2019-04-16
Citation
Journal of Innate Immunity, 2020, 12 (1), pp.90-102
ISSN
1662-811X
Publisher
Karger Publishers Open Access
Start Page
90
End Page
102
Journal / Book Title
Journal of Innate Immunity
Volume
12
Issue
1
Copyright Statement
© 2019 The Author(s)Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any dis-tribution of modified material requires written permission.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31266011
PII: 000500419
Subjects
Estrogen
Monocytes
Secretory leucoprotease inhibitor
microRNA
Publication Status
Published
Coverage Spatial
Switzerland
Date Publish Online
2019-07-02