Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma.

Abstract

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.

• Authors: N Wang, I Tabas, R Winchester, S Ravalli, L E Rabbani, A Tall
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 271 Issue 15 Pg. 8837-42 (Apr 12 1996) ISSN: 0021-9258 [Print] United States
• PMID: 8621523 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• Interleukin-8
• RNA, Messenger
• Cholesterol

Topics

• Arteriosclerosis (metabolism)
• Cells, Cultured
• Chemokine CCL2 (genetics)
• Cholesterol (metabolism)
• Foam Cells (metabolism)
• Gene Expression
• Humans
• In Situ Hybridization
• Interleukin-8 (biosynthesis)
• Macrophages (metabolism)
• Myocardium (metabolism)
• RNA, Messenger (genetics)
• Time Factors