title: Lipopolysaccharide activated phosphatidylcholine-specific phospholipase C and induced IL-8 and MCP-1 production in vascular endothelial cells.
abstract: Secretion of proinflammatory cytokines by lipopolysaccharide (LPS) activated vascular endothelial cells (VECs) contributes substantially to the pathogenesis of several inflammatory diseases such as atherosclerosis and septic shock. However, the mechanisms involved in this process are not well understood. Here, we investigated the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in LPS-induced IL-8 and MCP-1 production in VECs. The results showed that LPS elevated the level of PC-PLC and the production of IL-8 and MCP-1 in Human umbilical vein vascular endothelial cells (HUVECs). Blocking the function of PC-PLC by exploiting the neutralization antibody of PC-PLC or tricyclodecan-9-yl-xanthogenate (D609), an inhibitor of PC-PLC, significantly inhibited LPS-induced production of IL-8 and MCP-1 in HUVECs. Furthermore, the in vivo experimental results showed that the levels of PC-PLC, IL-8, and MCP-1 in the aortic endothelium and serum were increased in mice injected with LPS. The increased levels of these molecules were also inhibited by the treatment with D609. The data suggested that blocking PC-PLC function significantly inhibited LPS-induced IL-8 and MCP-1 production in cultured HUVECs and in vivo. PC-PLC might be a potential target for therapy in inflammation associated-diseases such as atherosclerosis.
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Hai Ying
authors.initials: HY
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Le
authors.initials: L
authors.lastname: Su
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shang Li
authors.initials: SL
authors.lastname: Zhang
authors.forename: Jun Ying
authors.initials: JY
authors.lastname: Miao
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009636:Norbornanes; D021381:Protein Transport / Q000187:drug effects; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D001952:Bridged-Ring Compounds; D018932:Chemokine CCL2; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C