IL-8 negatively regulates ABCA1 expression and cholesterol efflux via upregulating miR-183 in THP-1 macrophage-derived foam cells
Authors: Xiao-Er Tang
Xiao-Dan Xia
Chao-Ke Tang
Zhen-Wang Zhao
Heng Li
Guo-Jun Zhao
Xi-Long Zheng
Ling-Yan Chen
Journal: Cytokine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ABCA1; Atherosclerosis; Cholesterol efflux; IL-8; miR-183.
Affiliations: Department of Pathophysiology, Shaoyang University, Shaoyang, Hunan 422000, China., The Clinic Medical College, Guilin Medical University, No. 1 Zhiyuan Road, Guilin, Guangxi 541100, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China., Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr. N.W., Calgary, Alberta T2N 4N1, Canada., Department of Histology and Embryology, Guilin Medical University, Guilin, Guangxi 541004, China. Electronic address: ., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China. Electronic address: .

Abstract:  Objective: Previous studies suggest that IL-8 has an important role in the regulation of cholesterol efflux, but whether miRNAs are involved in this process is still unknown. The purpose of this study is to explore whether IL-8 promotes cholesterol accumulation by enhancing miR-183 expression in macrophages and its underlying mechanism. Methods and results: Treatment of THP-1 macrophage-derived foam cells with IL-8 decreased ABCA1 expression and cholesterol efflux. Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-183 was highly conserved during evolution and directly inhibited ABCA1 protein and mRNA expression by targeting ABCA1 3'UTR. MiR-183 directly regulated endogenous ABCA1 expression levels. Furthermore, IL-8 enhanced the expression of miR-183 and decrease ABCA1 expression. Cholesterol transport assays confirmed that IL-8 dramatically inhibited apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux by increasing miR-183 expression. In contrast, treatment with anti-IL-8 antibody reversed these effects. Conclusion: IL-8 enhances the expression of miR-183, which then inhibits ABCA1 expression and cholesterol efflux. Our studies suggest that the IL-8-miR-183-ABCA1 axis may play an intermediary role in the development of atherosclerosis. 

Retracted: No

PubPeer comments:
 Figure 3. This doesn t look too good. Left blot (D) is dose-dependence. Right blot (E) is time-dependence. This paper is part of a growing number of papers by the same senior author on topics related to lipid metabolism and atherosclerosis that contain questionable data and images. My suspicion is that the actin blot for figure 1C is actually a sharper version of the actin blots shown below but this goes beyond the resolution of my eyesight. ![file] ,