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Published on: July 26, 2017
MiRNA-181a regulates Toll-like receptor agonist-induced inflammatory response in human fibroblasts
J C Galicia1, A R Naqvi2, C-C Ko3
1Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.
Abstract:
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.
Insights
MicroRNAs regulate inflammation. This study shows microRNA-181a directly controls interleukin-8 production in dental pulp fibroblasts, revealing a new mechanism in inflammatory responses.
Area of Science:
- Immunology
- Molecular Biology
- Dental Research
Background:
- MicroRNAs (miRNAs) are key regulators of cytokine synthesis following Toll-like receptor (TLR) activation.
- Previous studies indicated differential expression of the miRNA-181 (miR-181) family in inflamed human dental pulps.
- Dental pulp fibroblasts, expressing TLR4/2, elevate cytokine production, such as interleukin-8 (IL-8), during inflammation.
Purpose of the Study:
- To investigate the role of the miR-181 family in the TLR agonist-induced inflammatory response in human dental pulp fibroblasts.
- To elucidate the regulatory mechanism of miR-181a on IL-8 expression in the context of inflammation.
Main Methods:
- Utilized an in-vitro model with primary human dental pulp fibroblasts.
- Stimulated fibroblasts with lipopolysaccharide from Porphyromonas gingivalis (Pg LPS), an oral pathogen.
- Measured IL-8 and miR-181 expression, performed in-silico analysis, and conducted dual-luciferase assays.
Main Results:
- Observed an inverse correlation between IL-8 and miR-181a expression levels.
- Identified and confirmed a miR-181a binding site on the 3' untranslated region (UTR) of IL-8.
- Demonstrated direct binding of miR-181a to the IL-8 3'UTR, modulating its expression.
Conclusions:
- MiR-181a directly targets and regulates the expression of IL-8, a critical inflammatory mediator.
- This finding establishes a novel regulatory pathway for IL-8 in dental pulp inflammation.
- Presents the first evidence of miR-181a controlling IL-8 production.
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