Toll-like receptor 4 (TLR4) is an innate immunity receptor predominantly expressed on myeloid cells and involved in the development of various diseases, many of them with complex genetics. Here we present data on functionality of single nucleotide polymorphism rs7873784 located in the 3'-untranslated region (3'-UTR) of TLR4 gene and associated with various pathologies involving chronic inflammation. We demonstrate that TLR4 3'-UTR strongly enhanced the activity of TLR4 promoter in U937 human monocytic cell line while minor rs7873784(C) allele created a binding site for transcription factor PU.1 (encoded by SPI1 gene), a known regulator of TLR4 expression. Increased binding of PU.1 further augmented the TLR4 transcription while PU.1 knockdown or complete disruption of the PU.1 binding site abrogated the effect. We hypothesize that additional functional PU.1 site may increase TLR4 expression in individuals carrying minor C variant of rs7873784 and modulate the development of certain pathologies, such as rheumatoid arthritis and type-2 diabetes mellitus.

中文翻译：

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与风湿性关节炎和2型糖尿病相关的SNP rs7873784的次要C等位基因与PU.1结合并增强TLR4表达。

Toll样受体4（TLR4）是一种先天免疫受体，主要在髓样细胞上表达，并参与多种疾病的发展，其中许多疾病具有复杂的遗传学。在这里，我们介绍位于TLR4基因3'-非翻译区（3'-UTR）的单核苷酸多态性rs7873784的功能数据，并涉及涉及慢性炎症的各种病理。我们证明，TLR4 3'-UTR在U937人单核细胞系中强烈增强TLR4启动子的活性，而次要rs7873784（C）等位基因为转录因子PU.1（由SPI1基因编码）创建了一个结合位点，该转录位点是TLR4的已知调节剂。表达。PU.1结合的增加进一步增强了TLR4的转录，而PU.1的敲低或PU.1结合位点的完全破坏则废除了该作用。