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

Joseph A. Cornicelli, Dustie Butteiger, Debra L. Rateri, Kathryn Welch, Alan Daugherty

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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 β-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 SRA 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-α and TGF-β, 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.

Original languageEnglish
Pages (from-to)376-383
Number of pages8
JournalJournal of Lipid Research
Issue number3
StatePublished - Mar 2000


  • CD36
  • Cytokines
  • LDL
  • Scavenger receptor
  • βVLDL

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


Dive into the research topics of 'Interleukin-4 augments acetylated LDL-induced cholesterol esterification in macrophages'. Together they form a unique fingerprint.

Cite this