MiRNA-181a regulates Toll-like receptor agonist-induced inflammatory response in human fibroblasts.
MicroRNAs (miRNAs) regulate the synthesis of cytokines in response to Toll-like receptor (TLR) activation. Our recent microarray study comparing normal and inflamed human dental pulps showed that miRNA-181 (miR-181) family is differentially expressed in the presence of inflammation. Prior studies have reported that the dental pulp, which is composed primarily of TLR4/2+ fibroblasts, expresses elevated levels of cytokines including interleukin-8 (IL-8) when inflamed. In this study, we employed an in-vitro model to determine the role of the miRNA-181 family in the TLR agonist-induced response in human fibroblasts. TLR4/2+ primary human dental pulp fibroblasts were stimulated with lipopolysaccharide from Porphyromonas gingivalis (Pg LPS), a known oral pathogen, and IL-8 and miR-181 expression measured. An inversely proportional relationship between IL-8 and miR-181a was observed. In-silico analysis identified a miR-181a-binding site on the 3' untranslated region (UTR) of IL-8, which was confirmed by dual-luciferase assays. MiR-181a directly binds to the 3'UTR of IL-8, an important inflammatory component of the immune response, and modulates its levels. This is the very first report demonstrating miR-181a regulation of IL-8.
Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
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Galicia
Department of Periodontics, College of Dentistry, University of Illinois, Chicago, IL, USA.
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Naqvi
Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
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CC
Ko
Department of Periodontics, College of Dentistry, University of Illinois, Chicago, IL, USA.
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Nares
1] Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA [2] Regional Center for Neurosensory Disorders, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
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Khan
D020413:3' Untranslated Regions; D001665:Binding Sites; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists
D020413:3' Untranslated Regions; D016209:Interleukin-8; D008070:Lipopolysaccharides; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D051193:Toll-Like Receptors