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Zhang, L.* ; Hofer, T.P. ; Zawada, A.M.* ; Rotter, B.* ; Krezdorn, N.* ; Nößner, E. ; Devaux, Y.* ; Heine, G.* ; Ziegler-Heitbrock, L.*

Epigenetics in non-classical monocytes support their pro-inflammatory gene expression.

Immunobiology 225:151958 (2020)
Postprint DOI
Open Access Green
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
ISSN (print) / ISBN 0171-2985
e-ISSN 1878-3279
Zeitschrift Immunobiology : Experimental and Clinical
Quellenangaben Band: 225, Heft: 3, Seiten: , Artikelnummer: 151958 Supplement: ,
Verlag Urban & Fischer
Verlagsort Hackerbrucke 6, 80335 Munich, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Immunoanalytics (IMA)