title: Microbial pattern recognition causes distinct functional micro-RNA signatures in primary human monocytes.
abstract: Micro-RNAs (miRNAs) are short, non-coding RNAs that regulate gene expression post transcriptionally. Several studies have demonstrated the relevance of miRNAs for a wide range of cellular mechanisms, however, the current knowledge on how miRNAs respond to relevant external stimuli, e.g. in disease scenarios is very limited. To generate a descriptive picture of the miRNA network associated to inflammatory responses, we quantified the levels of 330 miRNAs upon stimulation with a panel of pro-inflammatory components such as microbial pattern molecules (flagellin, diacylated lipopeptide lipopolysaccharide, muramyl dipeptide), infection with Listeria monocytogenes and TNF-α as pro-inflammatory control in primary human monocytes using real time PCR. As a result, we found distinct miRNA response clusters for each stimulus used. Additionally, we identified potential target genes of three selected miRNAs miR-129-5p, miR-146a and miR-378 which were part of PAMP-specific response clusters by transfecting THP1 monocytes with the corresponding pre- or anti-miRNAs and microfluidic PCR arrays. The miRNAs induced distinct transcriptomal signatures, e.g. overexpression of miRNA129-5p, which was selectively upregulated by the NOD2-elicitor MDP, led to an upregulation of DEFB1, IRAK1, FBXW7 and IKK γ (Nemo). Our findings on highly co-regulated clusters of miRNAs support the hypothesis that miRNAs act in functional groups. This study indicates that miRNAs play an important role in fine-tuning inflammatory mechanisms. Further investigation in the field of miRNA responses will help to understand their effects on gene expression and may close the regulatory gap between mRNA and protein expression in inflammatory diseases.
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University Kiel, Kiel, Schleswig-Holstein, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobs
authors.forename: Andreas
authors.initials: A
authors.lastname: Till
authors.forename: Nils
authors.initials: N
authors.lastname: Grabe
authors.forename: Christian
authors.initials: C
authors.lastname: Cordes
authors.forename: Susanna
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Kaiqin
authors.initials: K
authors.lastname: Lao
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
mesh_terms: D000328:Adult; D001686:Biological Phenomena / Q000235:genetics; D002478:Cells, Cultured; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000382:microbiology*; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D051192:Receptors, Pattern Recognition