期刊
GENES AND IMMUNITY
卷 15, 期 5, 页码 333-337出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2014.24
关键词
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资金
- National Institute for Dental and Craniofacial Research (NIDCR) [R01DE021052]
- NIDCR [T90DE021986]
- UNC School of Dentistry's Next Generation of Oral Health Researchers (NextGen)
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 m1RNA-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.
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