Regulation of Chronic Inflammation of Endothelial Cells by a Pro-Inflammatory Epoxyisoprostane Phospholipid

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Brackman, Abbie Kay
Heart disease; phospholipids; inflammation; atherosclerosis; endothelial
abstract description
Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), referred to as Ox-PAPC, accumulate in areas of chronic inflammation and regulate over 1000 genes in human aortic endothelial cells, affecting many pathways, including inflammation and monocyte recruitment. It was hypothesized that the most active component of Ox-PAPC, 1-palmitoyl-2-(5,6)-epoxyisoprostane E2-sn-glycero-3-phosphatidylcholine (PEIPC), binds with a mediating protein to activate a biological mechanism that triggers an upregulation of the gene that codes for monocyte chemotactic protein-1 (MCP-1). In this study, we tested and determined the effects of a candidate protein, glucose regulated protein 78 (GRP78) on PEIPC regulation of IL-8, HO-1, and MCP-1, representing the inflammatory, oxidative stress, and monocyte recruitment pathways in human aortic endothelial cells (HAEC). Binding of PEIPC to endothelial proteins was detected using biotin-tagged lipid and Western blotting, and the effect of GRP78 expression on gene regulation in HAECs was tested using RT-PCR. Additionally, we investigated if the mechanism of inflammation by pro-inflammatory cytokines (IL-1 003B2 and TNF- & #8733; or & prop;) is also mediated by GRP78. Our findings indicate that GRP78 has a role in PEIPC, IL-1β and TNF- & #8733; or & prop; regulation of the inflammatory pathway in HAEC, while also having a role in IL-1 003B2 and TNF- 003B2 regulation of the monocyte recruitment pathway.