EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells.

Weiling Leng,Ziwen Liang,Xinshou Ouyang,Xiaotian Lei,Hao Meng

doi:10.1155/2015/301562

Weiling Leng, Ziwen Liang + Show 3 more

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https://doi.org/10.1155/2015/301562

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Abstract

Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells.

Highlights

Endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number 074889, named as CXorf40A) has been identified by our research group from the genes with differential expression after stimulation of ECV304 cells with lipopolysaccharide (LPS) in 2004 [1, 2]; its biological function is less understood
The bioinformatics analysis reviewed that EOLA1 gene belongs to the activating signal cointegrator-1 (ASC-1) homology (ASCH) superfamily, which is frequently observed in many organisms [3, 4]
To further understand the biological function of EOLA1 in regulating inflammatory immune response, we focused on determining the subcellular distribution of EOLA1 and its efficacy in the regulation of LPS-induced inflammatory gene response including vascular cell adhesion molecule-1 (VCAM-1) in ECV304 cells

Summary

Introduction

Endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number 074889, named as CXorf40A) has been identified by our research group from the genes with differential expression after stimulation of ECV304 cells with lipopolysaccharide (LPS) in 2004 [1, 2]; its biological function is less understood. EOLA1 protein comprises 158 amino acids and has several glycosylation and phosphorylation sites and the helix-turn-helix motif without signal peptide and membrane spanning domain. These structural features indicate that EOLA1 is an intracellular protein and may interact with other unknown proteins in the cytoplasm and nucleus to regulate cell function. The bioinformatics analysis reviewed that EOLA1 gene belongs to the activating signal cointegrator-1 (ASC-1) homology (ASCH) superfamily, which is frequently observed in many organisms [3, 4]

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