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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1872-1880.)
© 1999 American Heart Association, Inc.

Vascular Biology

Transcriptional Inhibition by Interleukin-6 of the Class A Macrophage Scavenger Receptor in Macrophages Derived From Human Peripheral Monocytes and the THP-1 Monocytic Cell Line

Hai-Sun Liao; Akiyo Matsumoto; Hiroshige Itakura; Takefumi Doi; Makoto Honda; Tatsuhiko Kodama; Yong-Jian Geng

From the Cardiovascular and Pulmonary Research Institute (H.-S.L., Y.-J.G.), Allegheny University of the Health Sciences, Pittsburgh, Pa; the Division of Clinical Nutrition (A.M., H.I.), National Institute of Health and Nutrition, Tokyo, Japan; the Faculty of Pharmaceutical Sciences (T.D.), Osaka University, Osaka, Japan; and the Department of Molecular Biology and Medicine (H.-S.L., M.H., T.K.), Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan.

Correspondence to Yong-Jian Geng, MD, PhD, Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, 8^th Floor, South Tower, 320 E North Ave, Pittsburgh, PA 15212. E-mail ygeng{at}pgh.auhs.edu

Abstract—Expression of the class A macrophage scavenger receptor (MSR) contributes to the uptake of modified low density lipoproteins (LDL) by macrophages and transformation of these cells into lipid-laden foam cells, which characterize atherosclerosis. Many environmental factors, in particular, proinflammatory cytokines and growth factors, can exert regulatory effects on MSR expression, whereas intracellular accumulation of cholesterol itself does not influence MSR levels to any considerable extent. In the present study, by using an in vitro model, we examined whether stimulation with interleukin-6 (IL-6), an immunoregulatory, multipotential cytokine, modulates the expression and activities of the MSR in macrophages. When treated with IL-6, macrophages derived from peripheral monocytes and phorbol 12-myristate 13-acetate (PMA)–differentiated THP-1 monocytic cells showed significantly reduced uptake and/or binding of the MSR ligand, acetylated LDL. This effect was paralleled by a reduction in the expression of MSR protein and mRNA. Analysis of MSR promoter activity in THP-1 cells transfected with an MSR promoter–reporter gene construct demonstrated decreased activity of the MSR promoter in IL-6–treated THP-1 macrophages. Electrophoretic mobility gel shift assay also showed a reduction in the binding of a transcription factor to the MSR promoter AP-1/ets elements in IL-6–treated cells. Thus, exposure to IL-6 may inhibit expression of the class A MSR in differentiated macrophages at transcriptional levels. This result suggests that this cytokine may modulate foam cell formation during atherogenesis.

Key Words: scavenger receptors • atherosclerosis • cytokines • foam cells • lipoproteins

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