Abstract
Antigen presenting cells such as dendritic cells and macrophages have recently been detected in atherosclerotic plaques. Toll-like receptors expressed on the surface of these cells, have been implicated in ongoing inflammatory responses in the plaques. In this study, we investigated the anti-inflammatory effect of atorvastatin, a lipid lowering drug, via Toll-like receptor 4 (TLR4) in vitro, employing murine pro-B cell lines transfected with hTLR4/MD2 and MyD88/hTLR4/MD2 systems. The results showed that atorvastatin at 10 microM significantly attenuated NF-kappaB activation within 24 hours while at lower doses of 0.1 and 1 microM, treatment time had to be prolonged up to 48 hours for a significant inhibition to occur. The inhibition of NF-kappaB was also observed in a cell line cotransfected with MyD88 and TLR4 suggesting that the attenuation of NF-kappaB by atorvastatin occurred in a MyD88 dependent fashion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology
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Anticholesteremic Agents / pharmacology*
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Atherosclerosis / drug therapy
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Atherosclerosis / genetics
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Atherosclerosis / immunology
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Atherosclerosis / metabolism
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Atorvastatin
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Line
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dose-Response Relationship, Drug
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Heptanoic Acids / pharmacology*
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Humans
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Lymphocyte Antigen 96 / genetics
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Lymphocyte Antigen 96 / immunology
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Lymphocyte Antigen 96 / metabolism
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Myeloid Differentiation Factor 88 / genetics
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Myeloid Differentiation Factor 88 / immunology*
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Myeloid Differentiation Factor 88 / metabolism
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NF-kappa B / genetics
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NF-kappa B / immunology*
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NF-kappa B / metabolism
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Pyrroles / pharmacology*
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology*
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Toll-Like Receptor 4 / metabolism
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Transfection
Substances
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Anti-Inflammatory Agents
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Anticholesteremic Agents
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Heptanoic Acids
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LY96 protein, human
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Ly96 protein, mouse
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Lymphocyte Antigen 96
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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NF-kappa B
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Pyrroles
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TLR4 protein, human
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Atorvastatin