Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
|
| pubmed:dateCreated |
1996-6-20
|
| pubmed:abstractText |
In order to identify novel genes expressed in macrophage-derived foam cells, we used a multigene assay to examine the expression of genes in control versus cholesterol-loaded macrophages. We compared THP-1 macrophages incubated with or without acetylated LDL (acLDL) +/- acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor (compound 58035) for 20 h and assessed changes in mRNA of chemokines, growth factors, interleukins, and adhesion molecules. Among 49 genes examined, an increase in mRNA was observed only for interleukin 8 (IL-8) in THP-1 macrophages. Northern analysis confirmed a 3- to 4-fold increase of IL-8 mRNA and an enzyme-linked immunosorbent assay (ELISA) revealed a corresponding increase in IL-8 in conditioned medium. Oxidized LDL (oxLDL) also induced IL-8 mRNA, but native LDL had no effect. 58035 had a moderate effect on IL-8 induction by acLDL. AcLDL-induced IL-8 expression was concentration- and time-dependent. The time course of IL-8 induction paralleled that of cholesterol loading. MCP-1, a chemokine implicated in recruiting monocytes in atherogenesis, was also induced by acLDL. The induction of MCP-1, however, peaked at 1 h after addition of acLDL and returned to basal level by 20 h while IL-8 induction peaked at 8 h and was still 2-fold higher than basal level at 20 h. IL-8 induction was also observed in fresh human monocyte-derived macrophage cells treated with acLDL. Finally, immunohistochemistry and in situ hybridization studies using specimens of human coronary atheromas showed expression of IL-8 mRNA in a macrophage-rich area. We conclude that IL-8 is induced in macrophage foam cells as a response to cholesterol loading. The chemoattractant and/or mitogenic effects of IL-8 on neutrophils, T cells, smooth muscle, or vascular endothelial cells may contribute to the progression and complications of atherosclerosis.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
12
|
| pubmed:volume |
271
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
8837-42
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8621523-Arteriosclerosis,
pubmed-meshheading:8621523-Cells, Cultured,
pubmed-meshheading:8621523-Chemokine CCL2,
pubmed-meshheading:8621523-Cholesterol,
pubmed-meshheading:8621523-Foam Cells,
pubmed-meshheading:8621523-Gene Expression,
pubmed-meshheading:8621523-Humans,
pubmed-meshheading:8621523-In Situ Hybridization,
pubmed-meshheading:8621523-Interleukin-8,
pubmed-meshheading:8621523-Macrophages,
pubmed-meshheading:8621523-Myocardium,
pubmed-meshheading:8621523-RNA, Messenger,
pubmed-meshheading:8621523-Time Factors
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma.
|
| pubmed:affiliation |
Division of Molecular Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
|
| pubmed:publicationType |
Journal Article
|