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• W2000293251 abstract "Previous studies have shown that apoE (apolipoprotein E) expression in macrophages suppresses inflammatory responses; however, whether endogenously synthesized apoE acts intracellularly or after its secretion in suppressing macrophage inflammation remains unclear. The present study used the murine monocyte macrophage cell line RAW 264.7 to examine the influence of exogenous apoE on macrophage inflammatory responses induced by TLR (Toll-like receptor)-4 and TLR-3 agonists LPS (lipopolysaccharide) and poly(I-C) respectively. Results showed that exogenously added apoE suppressed the LPS and poly(I-C) induction of IL (interleukin)-6, IL-1β and TNF-α (tumour necrosis factor-α) secretion by RAW 264.7 cells. The mechanism was related to apoE suppression of TLR-agonist-induced phosphorylation of JNK (c-Jun N-terminal kinase) and c-Jun. A peptide containing the tandem repeat sequence of the receptor-binding domain of apoE, apoE-(141–155)2, was similarly effective in inhibiting LPS- and poly(I-C)-induced macrophage inflammatory responses. Reductive methylation of lysine residues in apoE, which abolished its receptor-binding capability without affecting its ability to interact with HSPGs (heparin sulfate proteoglycans), inhibited the ability of apoE to suppress macrophage responses to LPS, but had no effect on apoE suppression of poly(I-C)-induced macrophage activation. The ability of apoE to suppress poly(I-C)-induced pro-inflammatory cytokine production was abolished by heparinase treatment of RAW 264.7 cells to remove cell-surface HSPGs. Taken together, these results indicate that exogenous apoE inhibits macrophage inflammatory responses to TLR-4 and TLR-3 agonists through distinct mechanisms related to receptor and HSPG binding respectively, and that these inhibitory effects converged on suppression of JNK and c-Jun activation which are necessary for macrophage activation." @default.
• W2000293251 created "2016-06-24" @default.
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• W2000293251 date "2010-04-28" @default.
• W2000293251 modified "2023-10-18" @default.
• W2000293251 title "Apolipoprotein E inhibits Toll-like receptor (TLR)-3- and TLR-4-mediated macrophage activation through distinct mechanisms" @default.
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• W2000293251 doi "https://doi.org/10.1042/bj20100016" @default.
• W2000293251 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3050041" @default.
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