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Journal of Lipid Research, Vol. 47, 2259-2267, October 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

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

Mathijs Groeneweg^*, Edwin Kanters, Monique N. Vergouwe^*, Hilde Duerink^*, Georg Kraal, Marten H. Hofker^* and Menno P. J. de Winther^1,*

^* Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

Published, JLR Papers in Press, July 13, 2006.

¹ To whom correspondence should be addressed. e-mail: dewinther{at}gen.unimaas.nl

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-ß 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-B 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.

Supplementary key words cytokines • inflammation • modified LDL • lipopolysaccharide • RAW 264.7

Abbreviations: BMM, bone marrow-derived macrophage; CE, cholesteryl ester; IL-6, interleukin-6; LPS, lipopolysaccharide; NF-B, nuclear factor-B; oxLDL, oxidized LDL; qPCR, quantitative PCR; TNF, tumor necrosis factor

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