Differential expression of immunoregulatory genes in monocytes in response to Porphyromonas gingivalis and Escherichia coli lipopolysaccharide
Differential expression of immunoregulatory genes in monocytes in response to Porphyromonas gingivalis and Escherichia coli lipopolysaccharide
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DOI：
10.1111/j.1365-2249.2009.03920.x
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发表时间：
2009-06-01
影响因子：
4.6
通讯作者：
Preshaw, P. M.
中科院分区：
文献类型：
--
作者：
Barksby, H. E.;Nile, C. J.;Preshaw, P. M.
牙龈卟啉单胞菌脂多糖 (LPS)（菌株 W50）与 Toll 样受体 2 (TLR-2) 相互作用，导致细胞因子表达和炎症，从而在牙周病的发病机制中发挥关键作用。本研究的目的是研究人单核细胞系 (THP-1) 对牙龈卟啉单胞菌 LPS 的先天免疫反应的关键调节介质的基因表达，并将这些结果与使用 TLR-4 配体大肠杆菌 LPS 获得的结果进行比较。使用定制的 Taqman 低密度阵列对 45 种不同的细胞因子相关基因进行表达谱分析。两种类型的 LPS 均高度上调白细胞介素 (IL)-1 α 和 IL-1 β、IL-18 受体 (IL-18R)、IL-18R 辅助蛋白和 IL-1 家族 (IL-1F)9。 IL-1F6、IL-1F7 和 caspase-1 的表达水平不受任一 LPS 的影响。肿瘤坏死因子-α、IL-6、白血病抑制因子和 IL-32 基因也被两种 LPS 高度诱导。对于包括 CXC 趋化因子配体 5 (CXCL5) 在内的一部分基因，在 THP-1 单核细胞中，表达仅由大肠杆菌 LPS 诱导，或者与牙龈卟啉单胞菌 LPS 相比，大肠杆菌的上调程度更高。在树突状细胞中也观察到类似的表达模式。对导致 CXCL5 表达的信号通路的分析表明，支持差异反应的机制并不涉及 TLR-2 和 TLR-4 招募不同的接头蛋白，因此发生在受体-接头复合物的下游。我们的结论是，TLR-2 和 TLR-4 配体激活的信号通路的差异导致先天免疫反应的差异，这在牙周病等多种微生物疾病中可能很重要。
Porphyromonas gingivalis lipopolysaccharide (LPS) (strain W50) interacts with Toll-like receptor 2 (TLR-2) leading to cytokine expression and inflammation, and thereby plays a key role in the pathogenesis of periodontal disease. The aims of this study were to investigate gene expression of key regulatory mediators of innate immune responses in a human monocytic cell line (THP-1) to P. gingivalis LPS and to compare these results with those obtained using the TLR-4 ligand, Escherichia coli LPS. Custom-made Taqman low-density arrays were used for expression profiling of 45 different cytokine-related genes. Both types of LPS highly up-regulated interleukin (IL)-1 alpha and IL-1 beta, IL-18 receptor (IL-18R), IL-18R accessory protein and IL-1 family (IL-1F)9. Expression levels of IL-1F6, IL-1F7 and caspase-1 were unaltered by either LPS. Genes for tumour necrosis factor-alpha, IL-6, leukaemia inhibitory factor and IL-32 were also highly induced by both LPS. For a subset of genes, including CXC chemokine ligand 5 (CXCL5), expression was induced only by E. coli LPS or was up-regulated more highly by E. coli compared with P. gingivalis LPS in THP-1 monocytes. A similar expression pattern was also observed in dendritic cells. Analysis of signalling pathways which lead to CXCL5 expression indicated that the mechanisms underpinning the differential responses did not involve the recruitment of different adaptor proteins by TLR-2 and TLR-4, and therefore occur downstream of the receptor-adaptor complex. We conclude that differences in signalling pathways activated by TLR-2 and TLR-4 ligands lead to differential innate immune responses which may be important in polymicrobial diseases such as periodontal disease.