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.
- cholesterol homeostasis
- lipid metabolism
- p38 signaling pathway
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.