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Epigenetics in non-classical monocytes support their pro-inflammatory gene expression.
Immunobiology 225:151958 (2020)
Non-classical human monocytes are characterized by high-level expression of cytokines like TNF, but the mechanisms involved are elusive. We have identified miRNAs and CpG-methylation sites that are unique to non-classical monocytes, defined via CD14 and CD16 expression levels. For down-regulated miRNAs that are linked to up-regulated mRNAs the dominant gene ontology term was intracellular signal transduction. This included down-regulated miRNA-20a-5p and miRNA-106b-5p, which both are linked to increased mRNA for the TRIM8 signaling molecule. Methylation analysis revealed 16 hypo-methylated CpG sites upstream of 14 differentially increased mRNAs including 2 sites upstream of TRIM8. Consistent with a positive role in signal transduction, high TRIM8 levels went along with high basal TNF mRNA levels in non-classical monocytes. Since cytokine expression levels in monocytes strongly increase after stimulation with toll-like-receptor ligands, we have analyzed non-classical monocytes (defined via slan expression) after stimulation with lipopolysaccharide (LPS). LPS-stimulated cells continued to have low miRNA-20a and miRNA-106b and high TRIM8 mRNA levels and they showed a 10-fold increase in TNF mRNA. These data suggest that decreased miRNAs and CpG hypo-methylation is linked to enhanced expression of TRIM8 and that this can contribute to the increased TNF levels in non-classical human monocytes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Monocyte Subsets ; Signal Transduction ; Cytokine Production ; Nf-kappa B Pathway ; Next Generation Sequencing; Activated Kinase 1; Dendritic Cells; Human Blood; Rna-seq; Differential Expression; Dna Methylation; 6-sulfo Lacnac; Web Server; Tnf-alpha; Subsets
Language
english
Publication Year
2020
HGF-reported in Year
2020
ISSN (print) / ISBN
0171-2985
e-ISSN
1878-3279
Quellenangaben
Volume: 225,
Issue: 3,
Article Number: 151958
Publisher
Urban & Fischer
Publishing Place
Hackerbrucke 6, 80335 Munich, Germany
Reviewing status
Peer reviewed
Institute(s)
Institute of Virology (VIRO)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-502710-001
WOS ID
WOS:000539280500014
Scopus ID
85084747377
Erfassungsdatum
2020-05-25