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Interleukin 8 Inhibition Enhanced Cholesterol Efflux in Acetylated Low-Density Lipoprotein–Stimulated THP-1 Macrophages
  1. Yandong Chen, MM*,
  2. Zheng Wang, PhD,
  3. Lijun Zhou, PhD*
  1. From the *Department of Cardiology, The First Affiliated Hospital of Harbin Medical University; and †Department of Cardiology, Heilongjiang Provincial Hospital, Harbin, China.
  1. Received September 2, 2013, and in revised form November 30, 2013.
  2. Accepted for publication December 7, 2013.
  3. Reprints: Lijun Zhou, PhD, Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 15008, China. E-mail: lijunzhoubiopaper{at}163.com

Abstract

Cholesterol efflux plays a major role in antiatherogenesis, and modification of this process may provide a new therapeutic approach to cardiovascular disease. Interleukin 8 (IL-8) is implicated in various aspects of atherosclerosis. However, the effect of IL-8 on cholesterol efflux is still unclear. Here, we used human IL-8–neutralizing antibody to inhibit IL-8 and analyze the function of IL-8 in cholesterol efflux from acetylated low-density lipoprotein–loaded THP-1 macrophages. Acetylated low-density lipoprotein loading resulted in an approximately 2.5-fold increase in both the mRNA and protein levels of IL-8 in THP-1 macrophages, when compared with nonloaded THP-1 macrophages (P < 0.01). Five and 10 µg/mL of human IL-8–neutralizing antibody enhanced cholesterol efflux from THP-1–derived macrophages by 1.2- and 1.4-fold, respectively. Moreover, anti–IL-8–treated cells showed increased expression of peroxisome proliferator-activated γ, liver X receptor alpha, and ATP-binding cassette transporter A1 at both the mRNA and protein levels. Ten micromoles of SB203580, an inhibitor of p38, almost completely suppressed the production of IL-8 from acetylated low-density lipoprotein–loaded THP-1 macrophages and accelerated cholesterol efflux. Taken together, our results indicate that IL-8 exerts negative regulatory effects on cholesterol efflux from THP-1 cells and may thus represent a potential target for prevention and treatment of atherosclerosis.

Key Words
  • atherosclerosis
  • cholesterol homeostasis
  • cytokine
  • lipid metabolism
  • macrophages
  • p38 signaling pathway

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