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

Abstract

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-b 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-KB 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.-Groeneweg, M., E. Kanters, M. N. Vergouwe, H. Duerink, G. Kraal, M. H. Hofker, and M. P. J. de Winther. Lipopolysaccharide-induced gene expression in murine macrophages is enhanced by prior exposure to oxLDL.

Separation of cellular nonpolar neutral lipids by normal-phase chromatography and analysis by electrospray ionization mass spectrometry

“…The recycling of cholesterol and intracellular cholesterol trafficking involve the action of CE hydrolase as well as ACAT1 in most cells (3). Toll-like receptor 4 is known to play an important role in changing macrophages into foam cells, which is thought to be a critical event in atherosclerosis (33). The accumulation of lipids within these macrophages is regulated by a number of enzymes, including fatty acid binding proteins and ACAT1.…”

Resistin-Like Molecule β Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis Development

“…It is well known that atherosclerosis develops through multiple processes, among which foam cell formation is a key event, because it leads to the secretion of inflammatory cytokines 24 and plaque instability. 25 It was revealed in vitro that RELMβ induced macrophages to induce NF-κB signaling and express inflammatory cytokines, lipid uptake, and also promoted their transformation into foam cells.…”

Macrophage Secretory Phospholipase A2 Group X Enhances Anti-inflammatory Responses, Promotes Lipid Accumulation, and Contributes to Aberrant Lung Pathology

“…After a 4-h adherence period, 25 g/ml LDL or oxLDL was added to the medium. The cells were incubated for 24 h after which they were washed, lifted, and processed for HPTLC as described previously (14).…”

“…sPLA 2 produces free fatty acids and lysophospholipids, important second messengers in cell signaling and signal transduction, by hydrolyzing glycerophospholipids present in cell membranes and plasma lipoproteins. sPLA 2 can be distinguished from other PLA 2 by their low molecular mass (13)(14)(15)(16)(17)(18), their high disulfide bond content (6 -8 bridges), and the requirement for millimolar concentrations of Ca 2ϩ for catalysis. Among the different sPLA 2 , the group X sPLA 2 (sPLA 2 -X) is the most potent in hydrolyzing phospholipids with different polar head groups and fatty acids (1,2).…”