Interleukin 8 inhibition enhanced cholesterol efflux in acetylated low-density lipoprotein-stimulated THP-1 macrophages.
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.
From the *Department of Cardiology, The First Affiliated Hospital of Harbin Medical University; and †Department of Cardiology, Heilongjiang Provincial Hospital, Harbin, China.
Yandong
Y
Chen
Zheng
Z
Wang
Lijun
L
Zhou
D000107:Acetylation; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*
D016209:Interleukin-8; D008077:Lipoproteins, LDL; D002784:Cholesterol