Hierarchical gene expression profiles of HUVEC stimulated by different lipid A structures obtained from Porphyromonas gingivalis and Escherichia coli
Hierarchical gene expression profiles of HUVEC stimulated by different lipid A structures obtained from Porphyromonas gingivalis and Escherichia coli
复制标题
DOI：
10.1111/j.1462-5822.2006.00849.x
复制
发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Darveau, Richard P.
中科院分区：
文献类型：
--
作者：
Chen, Casey;Coats, Stephen R.;Darveau, Richard P.
脂质A结构变体引发独特的内皮细胞基因表达的能力通过使用Affyellow全基因组芯片测量人脐带静脉内皮细胞（HUVEC）中的全局基因表达谱来检查。从牙龈卟啉单胞菌获得的两种脂质A结构变体命名为PgLPS（1435/1449）和PgLPS（1690），以及从大肠杆菌野生型和大肠杆菌野生型获得的LPS。colimsbB突变体（脂质A中缺失肉豆蔻酸）。这些脂质A结构中的每一个都已被证明与TLR 4相互作用;然而，PgLPS（1435/1449）和E. coli msbB LPS是TLR 4的拮抗剂，而PgLPS（1690）和野生型E. coli LPS是TLR 4激动剂。结果表明，PgLPS（1435/1449）和PgLPS（1690）与E. coli msbB LPS激活了这些基因的一个子集，这些基因在对E. coli野生型LPS。此外，响应于不同脂质A结构形式表达的基因子集是那些被野生型E. coliLPS显示TLR 4依赖的内皮细胞基因激活的层次。观察到弱TLR 4激动剂PgLPS（1690）的独特基因表达谱，其代表内皮细胞基因活化中的TLR 4层级。
The ability of lipid A structural variants to elicit unique endothelial cell gene expression was examined by measuring global gene expression profiles in human umbilical cord vein endothelial cells (HUVEC) using Affymetrix full genome chips. Two lipid A structural variants obtained from Porphyromonas gingivalis designated PgLPS(1435/1449) and PgLPS(1690) as well as LPS obtained from Escherichia coli wild type and an E. coli msbB mutant (missing myristic acid in the lipid A) were examined. Each of these lipid A structures has been shown to interact with TLR4; however, PgLPS(1435/1449) and E. coli msbB LPS have been shown to be TLR4 antagonists while PgLPS(1690) and wild-type E. coli LPS are TLR4 agonists. It was found that PgLPS(1435/1449) and PgLPS(1690) as well as E. coli msbB LPS activated a subset of those genes significantly transcribed in response to E. coli wild-type LPS. Furthermore, the subset of genes expressed in response to the different lipid A structural forms were those most significantly activated by wild-type E. coli LPS demonstrating a hierarchy in TLR4-dependent endothelial cell gene activation. A unique gene expression profile for the weak TLR4 agonist PgLPS(1690) was observed and represents a TLR4 hierarchy in endothelial cell gene activation.