Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL

Uptake of modified lipoproteins by macrophages results in the formation of foam cells. We investigated how foam cell formation affects the inflammatory response of macrophages. Murine bone marrow-derived macrophages were treated with oxidized LDL (oxLDL) to induce foam cell formation. Subsequently,...

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Main Authors: Mathijs Groeneweg, Edwin Kanters, Monique N. Vergouwe, Hilde Duerink, Georg Kraal, Marten H. Hofker, Menno P.J. de Winther
Format: Article
Language:English
Published: Elsevier 2006-10-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520434133
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author Mathijs Groeneweg
Edwin Kanters
Monique N. Vergouwe
Hilde Duerink
Georg Kraal
Marten H. Hofker
Menno P.J. de Winther
author_facet Mathijs Groeneweg
Edwin Kanters
Monique N. Vergouwe
Hilde Duerink
Georg Kraal
Marten H. Hofker
Menno P.J. de Winther
author_sort Mathijs Groeneweg
collection DOAJ
description Uptake of modified lipoproteins by macrophages results in the formation of foam cells. We investigated how foam cell formation affects the inflammatory response of macrophages. Murine bone marrow-derived macrophages were treated with oxidized LDL (oxLDL) to induce foam cell formation. Subsequently, the foam cells were activated with lipopolysaccharide (LPS), and the expression of lipid metabolism and inflammatory genes was analyzed. Furthermore, gene expression profiles of foam cells were analyzed using a microarray. We found that prior exposure to oxLDL resulted in enhanced LPS-induced tumor necrosis factor (TNF) and interleukin-6 (IL-6) gene expression, whereas the expression of the anti-inflammatory cytokine IL-10 and interferon-β was decreased in foam cells. Also, LPS-induced cytokine secretion of TNF, IL-6, and IL-12 was enhanced, whereas secretion of IL-10 was strongly reduced after oxLDL preincubation. Microarray experiments showed that the overall inflammatory response induced by LPS was enhanced by oxLDL loading of the macrophages. Moreover, oxLDL loading was shown to result in increased nuclear factor-κB activation. In conclusion, our experiments show that the inflammatory response to LPS is enhanced by loading of macrophages with oxLDL. These data demonstrate that foam cell formation may augment the inflammatory response of macrophages during atherogenesis, possibly in an IL-10-dependent manner.
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spelling doaj.art-ea62037277284d128a1181159c8ef8842022-12-21T20:27:03ZengElsevierJournal of Lipid Research0022-22752006-10-01471022592267Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDLMathijs Groeneweg0Edwin Kanters1Monique N. Vergouwe2Hilde Duerink3Georg Kraal4Marten H. Hofker5Menno P.J. de Winther6Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The NetherlandsDepartment of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The NetherlandsDepartment of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The NetherlandsDepartment of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The NetherlandsDepartment of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The NetherlandsDepartment of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The NetherlandsUptake of modified lipoproteins by macrophages results in the formation of foam cells. We investigated how foam cell formation affects the inflammatory response of macrophages. Murine bone marrow-derived macrophages were treated with oxidized LDL (oxLDL) to induce foam cell formation. Subsequently, the foam cells were activated with lipopolysaccharide (LPS), and the expression of lipid metabolism and inflammatory genes was analyzed. Furthermore, gene expression profiles of foam cells were analyzed using a microarray. We found that prior exposure to oxLDL resulted in enhanced LPS-induced tumor necrosis factor (TNF) and interleukin-6 (IL-6) gene expression, whereas the expression of the anti-inflammatory cytokine IL-10 and interferon-β was decreased in foam cells. Also, LPS-induced cytokine secretion of TNF, IL-6, and IL-12 was enhanced, whereas secretion of IL-10 was strongly reduced after oxLDL preincubation. Microarray experiments showed that the overall inflammatory response induced by LPS was enhanced by oxLDL loading of the macrophages. Moreover, oxLDL loading was shown to result in increased nuclear factor-κB activation. In conclusion, our experiments show that the inflammatory response to LPS is enhanced by loading of macrophages with oxLDL. These data demonstrate that foam cell formation may augment the inflammatory response of macrophages during atherogenesis, possibly in an IL-10-dependent manner.http://www.sciencedirect.com/science/article/pii/S0022227520434133cytokinesinflammationmodified LDLlipopolysaccharideRAW 264.7
spellingShingle Mathijs Groeneweg
Edwin Kanters
Monique N. Vergouwe
Hilde Duerink
Georg Kraal
Marten H. Hofker
Menno P.J. de Winther
Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL
Journal of Lipid Research
cytokines
inflammation
modified LDL
lipopolysaccharide
RAW 264.7
title Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL
title_full Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL
title_fullStr Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL
title_full_unstemmed Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL
title_short Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL
title_sort lipopolysaccharide induced gene expression in murine macrophages is enhanced by prior exposure to oxldl
topic cytokines
inflammation
modified LDL
lipopolysaccharide
RAW 264.7
url http://www.sciencedirect.com/science/article/pii/S0022227520434133
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