Epistatic effect of TLR-1, -6 and -10 polymorphisms on organic dust-mediated cytokine response.
Epistatic effect of TLR-1, -6 and -10 polymorphisms on organic dust-mediated cytokine response.
复制标题
TLR-1、-6和-10多态性对有机粉尘介导的细胞因子反应的上位效应。
DOI：
10.1038/gene.2016.51
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发表时间：
2017
影响因子：
5
通讯作者：
LeVan,TD
中科院分区：
文献类型：
--
作者：
Smith,LM;Weissenburger-Moser,LA;Heires,AJ;Bailey,KL;Romberger,DJ;LeVan,TD
暴露于农业环境中的有机粉尘与炎症性呼吸道疾病有关。有机粉尘中的致病因子包括病毒、微生物和真菌成分，这些成分被Toll样受体（TLR）家族识别，并驱动宿主的先天性和适应性反应。本研究的目的是确定农业工人对有机粉尘的反应是否依赖于TLR 10-TLR 1-TLR 6基因簇的多态性。我们刺激全血509农业工人与有机粉尘，三酰基脂肽N-棕榈酰-S-二棕榈酰甘油Cys-Ser-（Lys）4（Pam 3CSK 4）和二酰基脂肽肽聚糖。几种标记多态性和单倍型赋予了对有机粉尘的高反应性，增加了白细胞介素-6（IL-6; P< 0.005）的分泌，但没有肿瘤坏死因子-α（TNF-α）的分泌。我们的结论是，TLR 10-TLR 1-TLR 6基因簇的遗传变异介导了对有机粉尘的反应，但表明IL-6和TNF-α的信号通路不同。这些研究为TLR 10-TLR 1-TLR 6基因簇的作用和对有机粉尘的先天免疫反应提供了新的见解。
Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of Toll-like receptors (TLRs) and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys–Ser–(Lys) 4 (Pam3CSK4) and the diacyl-lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in interleukin-6 (IL-6; P< 0.005), but not tumor necrosis factor-α (TNF-α), secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust.