title: EOLA1 protects lipopolysaccharide induced IL-6 production and apoptosis by regulation of MT2A in human umbilical vein endothelial cells.
abstract: Endothelial cell (EC) injury or dysfunction is believed to be mediated at least in part by lipopolysaccharide (LPS). Recent studies have shown that LPS induces apoptosis in different types of endothelium, including HUVEC. Previously we used EOLA1 (endothelial-overexpressed LPS-associated factor 1) cDNA as a bait and performed a yeast two-hybrid screening of a human liver cDNA library and identified metallothionein 2a (MT2a) as the associated protein. EOLA1 protein plays a role as a signal transduction factor. But the mechanism of EOLA1 mediated the protection of cell production of IL-6 and apopotosis in HUVEC is not known. MT2a is expressed in many kinds of cells and plays a role in inflammation. In this study, we demonstrated that LPS could induce EOLA1 expression in time-dependent and apparently contributed to the inhibition of IL-6 production and apoptosis induced by LPS treatment. We also found that deletion of EOLA1 promoted IL-6 production and apoptosis in the treatment of LPS in HUVEC. Furthermore, we demonstrated that MT2a was activated by LPS, and played a key role in LPS-induced IL-6 expression in HUVEC. We further provided the evidence that EOLA1 functioned as a negative regulator for LPS response by regulation of MT2a. These findings suggest that EOLA1 may have an important regulatory role during EC inflammatory responses.
authors.affiliation: Burn and Plastic Surgery Department of the First Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Liu
authors.forename: Hairong
authors.initials: H
authors.lastname: Liu
authors.forename: Wenhai
authors.initials: W
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*
chemical_list: C495142:EOLA1 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; C491053:MT2A protein, human; D008565:Membrane Proteins; D008668:Metallothionein