MiRNA-181a regulates Toll-like receptor agonist-induced inflammatory response in human fibroblasts.
MiRNA-181a regulates Toll-like receptor agonist-induced inflammatory response in human fibroblasts.
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miRNA-181a调节人的成纤维细胞中的Toll样受体激动剂诱导的炎症反应。
DOI：
10.1038/gene.2014.24
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发表时间：
2014-07
影响因子：
5
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中科院分区：
文献类型：
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微小RNA（miRNA）调节响应于Toll样受体（TLR）激活的细胞因子的合成。我们最近的微阵列研究比较了正常和炎症的人类牙髓，发现miRNA-181（miR-181）家族在炎症存在时差异表达。先前的研究已经报道，主要由TLR 4/2+成纤维细胞组成的牙髓在发炎时表达升高水平的细胞因子，包括白细胞介素-8（IL-8）。在这项研究中，我们采用体外模型来确定miRNA 181家族在TLR激动剂诱导的人成纤维细胞反应中的作用。用来自牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg LPS）的脂多糖（一种已知的口腔病原体）刺激TLR 4/2+原代人牙髓成纤维细胞，并测量IL-8和miR-181表达。观察到IL-8和miR-181 a之间呈反比关系。计算机模拟分析在IL-8的3′UTR上鉴定了miR-181 a结合位点，这通过双荧光素酶测定得到证实。MiR-181 a直接与IL-8的3′UTR结合，IL-8是免疫应答的重要炎症组分，并调节其水平。这是第一份证明miR-181 a调节IL-8的报告。
MicroRNAs (miRNA) 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′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.