Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Diverse Bacteria Promote Macrophage Foam Cell Formation Via Toll-Like Receptor-Dependent Lipid Body Biosynthesis
Giovanna NicolaouAlison H GoodallClett Erridge
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JOURNAL OPEN ACCESS

2012 Volume 19 Issue 2 Pages 137-148

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Abstract

Aim: Atherosclerotic lesions contain DNA signatures from a wide variety of bacteria, although little is known of how exposure to these organisms may modulate the accumulation of lipids in macrophages.
Methods: To address this, a panel of nine bacteria representing those most frequently reported to be present in human atheroma were examined for their potential to promote lipid accumulation in human primary monocytes and murine J774 macrophages.
Results: All bacteria examined, and defined stimulants of Toll-like receptors (TLRs) 2, 3, 4, 5 and 9, induced lipid body formation and cholesterol ester accumulation in a dose-dependent manner. The mechanisms of bacteria-mediated foam cell formation were found to be dependent on TLR2 and/or TLR4 signalling, but independent of lipoprotein oxidation pathways, since lipid accumulation was significantly inhibited by the TLR4 inhibitors polymyxin-B and TAK-242, or the TLR2 and TLR4 inhibitor oxidised palmitoyl-arachidonyl-phosphatidyl-choline, but not by the scavenger receptor blocker polyinosinic acid or the antioxidant butylated hydroxytoluene. A number of genes involved in lipid body biosynthesis, including perilipin-A, stearoyl-coenzyme-A desaturase 1, fatty acid synthase and HMG-CoA reductase were upregulated in response to TLR4 stimulation.
Conclusions: The bacterial debris observed in human atheroma, which is currently considered to be harmless, may have potential to contribute to disease progression via TLR-dependent lipid body formation in macrophages.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 - 継承 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja
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