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Inflammatory stress increases unmodified LDL uptake via LDL receptor: an alternative pathway for macrophage foam-cell formation

Ye, Qiang, Chen, Yaxi, Lei, Han, Liu, Qing, Moorhead, John F., Varghese, Zac, Ruan, Xiong Z.·2009·Inflammation Research

Abstract

Objective To investigate if inflammatory stress increases intracellular accumulation of unmodified low-density lipoprotein (LDL) in human monocyte cell line (THP-1) macrophages by disrupting the sterol regulatory element binding proteins (SREBPs) cleavage-activating protein (SCAP)-SREBP2-mediated feedback regulation of LDL receptor. Materials and methods THP-1 macrophages were incubated in serum-free medium in the absence or presence of LDL alone, LDL plus lipopolysaccharide (LPS) and LPS alone, then intracellular cholesterol content, tumor necrosis factor alpha level in the supernatants, mRNA and protein expression of LDL receptor, and SREBP2 and SCAP in the treated cells were assessed by Oil Red O staining, cholesterol enzymatic assay, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and Western blotting analysis, respectively. Results We demonstrated that LPS enhanced transformation of THP-1 macrophages into foam cells by increased uptake of unmodified LDL as evidenced by Oil Red O staining and direct assay of intracellular cholesterol. In the absence of LPS, 25 microg/ml LDL decreased LDL receptor mRNA and protein expression (p Conclusion The implication of these findings is that inflammatory stress may contribute to intracellular LDL accumulation in THP-1 macrophages without previous modification of LDL.

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Crossref · 10.1007/s00011-009-0052-4

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Metadata

Authors
Ye, Q., Chen, Y., Lei, H., Liu, Q., Moorhead, J. F., Varghese, Z., & Ruan, X. Z.
Venue
Inflammation Research
Published
2009-06-17
Volume
58
Issue
11
Pages
809-818
ISSN
  • 1023-3830
  • 1420-908X
Cited by
47
References
0
Language
en

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