Open AccessHierarchical gene expression profiles of HUVEC stimulated by different lipid A structures obtained from Porphyromonas gingivalis and Escherichia coli
Author(s) -
Chen Casey,
Coats Stephen R.,
Bumgarner Roger E.,
Darveau Richard P.
Publication year - 2007
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2006.00849.x
Subject(s) - biology , escherichia coli , lipid a , tlr4 , porphyromonas gingivalis , lipopolysaccharide , human umbilical vein endothelial cell , gene , microbiology and biotechnology , gene expression , umbilical vein , biochemistry , bacteria , signal transduction , immunology , genetics , in vitro
Summary 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.