This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liao, H.-S. Articles by Geng, Y.-J. Search for Related Content PubMed PubMed Citation Articles by Liao, H.-S. Articles by Geng, Y.-J. Related Collections Pathophysiology Growth factors/cytokines Physiological and pathological control of gene expression Lipid and lipoprotein metabolism

(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

This article has been cited by other articles:

				N. Takeda, I. Manabe, T. Shindo, H. Iwata, S. Iimuro, H. Kagechika, K. Shudo, and R. Nagai Synthetic Retinoid Am80 Reduces Scavenger Receptor Expression and Atherosclerosis in Mice by Inhibiting IL-6 Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1177 - 1183. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]

				A. Daugherty, N. R. Webb, D. L. Rateri, and V. L. King Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis J. Lipid Res., September 1, 2005; 46(9): 1812 - 1822. [Abstract] [Full Text] [PDF]

				E. M. Fach, L.-A. Garulacan, J. Gao, Q. Xiao, S. M. Storm, Y. P. Dubaquie, S. A. Hefta, and G. J. Opiteck In Vitro Biomarker Discovery for Atherosclerosis by Proteomics Mol. Cell. Proteomics, December 1, 2004; 3(12): 1200 - 1210. [Abstract] [Full Text] [PDF]

				G. Yang, J. Addai, W.-h. Tian, A. Frolov, T. M. Wheeler, and T. C. Thompson Reduced Infiltration of Class A Scavenger Receptor Positive Antigen-Presenting Cells Is Associated with Prostate Cancer Progression Cancer Res., March 15, 2004; 64(6): 2076 - 2082. [Abstract] [Full Text] [PDF]

				P. Foka, S. A. Irvine, F. Kockar, and D. P. Ramji Interleukin-6 represses the transcription of the CCAAT/enhancer binding protein-{alpha} gene in hepatoma cells by inhibiting its ability to autoactivate the proximal promoter region Nucleic Acids Res., December 1, 2003; 31(23): 6722 - 6732. [Abstract] [Full Text] [PDF]

				J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]

				G. K. Hansson Immune Mechanisms in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1876 - 1890. [Abstract] [Full Text] [PDF]