HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Cornicelli, J. A. Articles by Daugherty, A. Search for Related Content PubMed PubMed Citation Articles by Cornicelli, J. A. Articles by Daugherty, A. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 376-383, March 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Interleukin-4 augments acetylated LDL-induced cholesterol esterification in macrophages

Correspondence to: Joseph A. Cornicelli

Correspondence to: Alan Daugherty

Activated subpopulations of lymphocytes and mast cells have been detected in atherosclerotic lesions. Interleukin-4 (IL-4) is a prominent cytokine released during activation of both cell types and its transcripts have been detected in both human and mouse atherosclerotic lesions. To define whether this local release of IL-4 influences macrophage lipid metabolism, we examined the effects of this cytokine on intracellular cholesterol esterification during incubation with modified low density lipoprotein (LDL). IL-4 greatly augmented cholesterol esterification induced by acetylated LDL (AcLDL) in both mouse peritoneal macrophages and the murine macrophage cell line, J774. This augmentation was maximal at a concentration of 1 ng/ml after incubation for 48 h. This was not a generalized effect on lipoprotein metabolism as IL-4 had no effect on cholesterol esterification in the presence of either LDL or ß-VLDL. Determination of binding isotherms demonstrated that IL-4 increased the number of cell surface binding sites for AcLDL. The IL-4-augmented AcLDL-induced cholesterol esterification was attenuated by the scavenger receptor class A (SR-A) antagonist, fucoidan, and the anti-mouse SR-A monoclonal antibody, 2F8.

These data, combined with the known receptor specificity of AcLDL interactions, imply a role of SR-A in the IL-4 induced responses. Two cytokines that have been demonstrated previously to down-regulate SR-A, TNF- and TGF-ß, antagonized the IL-4-induced augmentation of cholesterol esterification. Therefore, local release of IL-4 within atherosclerotic lesions could have a profound effect on macrophage lipid metabolism and the subsequent atherogenic process.—Cornicelli, J. A., D. Butteiger, D. L. Rateri, K. Welch, and A. Daugherty. Interleukin-4 augments acetylated LDL-induced cholesterol esterification in macrophages. J. Lipid Res. 2000. 41: 376;–383.

Supplementary key words: scavenger receptor, CD36, LDL, ß-VLDL, cytokines

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Rogers, S. Burchat, J. Gage, M. Hasu, M. Thabet, L. Wilcox, T. A. Ramsamy, and S. C. Whitman Deficiency of invariant V{alpha}14 natural killer T cells decreases atherosclerosis in LDL receptor null mice Cardiovasc Res, April 1, 2008; 78(1): 167 - 174. [Abstract] [Full Text] [PDF]

				V. L. King, L. A. Cassis, and A. Daugherty Interleukin-4 Does Not Influence Development of Hypercholesterolemia or Angiotensin II-Induced Atherosclerotic Lesions in Mice Am. J. Pathol., December 1, 2007; 171(6): 2040 - 2047. [Abstract] [Full Text] [PDF]

				F. O. Martinez, S. Gordon, M. Locati, and A. Mantovani Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression J. Immunol., November 15, 2006; 177(10): 7303 - 7311. [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]

				B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [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]

				S. R. Post, C. Gass, S. Rice, D. Nikolic, H. Crump, and G. R. Post Class A scavenger receptors mediate cell adhesion via activation of Gi/o and formation of focal adhesion complexes J. Lipid Res., November 1, 2002; 43(11): 1829 - 1836. [Abstract] [Full Text] [PDF]

				V. L. King, S. J. Szilvassy, and A. Daugherty Interleukin-4 Deficiency Decreases Atherosclerotic Lesion Formation in a Site-Specific Manner in Female LDL Receptor-/- Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2002; 22(3): 456 - 461. [Abstract] [Full Text] [PDF]

				S. C. Whitman, P. Ravisankar, H. Elam, and A. Daugherty Exogenous Interferon-{{gamma}} Enhances Atherosclerosis in Apolipoprotein E-/- Mice Am. J. Pathol., December 1, 2000; 157(6): 1819 - 1824. [Abstract] [Full Text] [PDF]

				A. Daugherty, S. C. Whitman, A. E. Block, and D. L. Rateri Polymorphism of class A scavenger receptors in C57BL/6 mice J. Lipid Res., October 1, 2000; 41(10): 1568 - 1577. [Abstract] [Full Text]

				S. C. Whitman, A. Daugherty, and S. R. Post Regulation of acetylated low density lipoprotein uptake in macrophages by pertussis toxin-sensitive G proteins J. Lipid Res., May 1, 2000; 41(5): 807 - 813. [Abstract] [Full Text]