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- W4313381922 abstract "Abstract Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key negative regulator of lipid uptake through low-density lipoprotein (LDL) receptor (LDLR), and has recently been implicated in regulating cytokine production during sepsis. We hypothesize that PCSK9 affects cytokine production by regulating hepatic LDLR-mediated uptake of bacterial lipids, such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and that this uptake is LDL-dependent. Methods HepG2 cells were cultured in media containing normal serum or lipoprotein-deficient serum (LPDS), and pre-treated with recombinant human PCSK9 or control, and with control IgG, or anti-LDLR antibody. HepG2 cells were also cultured in LPDS with add-back of increasing LDL concentrations. Cells were then treated for 24 h with fluorescent LPS or LTA, or controls. Media was collected for cytokine assays, and flow cytometry was performed to quantify LPS or LTA uptake by measuring fluorescence. Results HepG2 cells pre-treated with recombinant PCSK9 or anti-LDLR antibody had significantly decreased fluorescent LPS and LTA uptake compared to controls when cultured in normal serum. Furthermore, cells pre-treated with both anti-LDLR antibody and PCSK9 showed similar uptake as cells treated with anti-LDLR antibody alone. Neither anti-LDLR antibody nor PCSK9 had any effect on cells cultured in LPDS, but LDL add-back dose-dependently increased uptake of both LPS and LTA. Varying uptake of LPS and LTA did not affect secretion of IL-6, IL-8, IL-10, or IL-17 by HepG2 cells. Conclusion Bacterial lipid uptake by HepG2 cells through LDLR requires LDL, and is negatively regulated by PCSK9, but does not affect cytokine production by these cells." @default.
- W4313381922 created "2023-01-06" @default.
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- W4313381922 date "2017-05-01" @default.
- W4313381922 modified "2023-09-27" @default.
- W4313381922 title "PCSK9 regulates LDL-dependent uptake of bacterial lipids by HepG2 cells through LDL receptor" @default.
- W4313381922 doi "https://doi.org/10.4049/jimmunol.198.supp.216.12" @default.
- W4313381922 hasPublicationYear "2017" @default.
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