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A more recent version of this article appeared on October 1, 2006

Papers In Press, published online ahead of print July 13, 2006
J. Lipid Res., doi:10.1194/jlr.M600181-JLR200
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Submitted on April 21, 2006
Revised on June 27, 2006
Accepted on July 13, 2006

LPS 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

Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht 6229ER

Corresponding Author: 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 low density lipoproteins (oxLDL) to induce foam cell formation. Subsequently, the foam cells were activated with LPS and expression of lipid metabolism and inflammatory genes was analyzed. Furthermore, gene expression profiles of foam cells were analyzed using microarray. We found that prior exposure to oxLDL resulted in an enhanced LPS induced TNF and IL-6 gene expression, whereas the expression of the anti-inflammatory cytokine IL-10 and IFN-ß were decreased in foam cells. Also, LPS induced cytokine secretion of TNF, IL-6 and IL-12 was enhanced, while 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 NF-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.


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