Lipoxin A4 promotes ABCA1 expression and cholesterol efflux through the LXRα signaling pathway in THP-1 macrophage-derived foam cells.
Adenosine triphosphate-binding cassette transporter A1 (ABCA1) is a crucial cholesterol transporter and plays a central role in the high density lipoproteins (HDL) cholesterol metabolism and lipid clearance from the foam cell. Lipoxin A4 (LXA4) is an endogenous lipid mediator that requires cell-cell interaction or cell-platelet interaction for its synthesis. The roles of LXA4 on inflammatory responses are well described, while its effects on mediating ABCA1 and underlying mechanisms remain unclear. In this study, we showed that LXA4 significantly increases expression of ABCA1 and LXRα in a dose-dependent manner in THP-1 macrophage-derived foam cells. Cellular cholesterol content was decreased while cholesterol efflux was increased by LXA4 treatment. However, after short interfering RNA of LXRα, the effects of LXA4 on ABCA1 expression and cholesterol metabolism were significantly abolished. These results provide evidence that LXA4 increases ABCA1 expression and promotes cholesterol efflux through LXRα pathway in THP-1 macrophage-derived foam cells.
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Yan-Hua
YH
Sha
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Yan-Wei
YW
Hu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Ji-Juan
JJ
Gao
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Yan-Chao
YC
Wang
Department of Anesthesiology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Xin
X
Ma
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Yu-Rong
YR
Qiu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Shu-Fen
SF
Li
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Jia-Yi
JY
Zhao
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Chuan
C
Huang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Jing-Jing
JJ
Zhao
Department of Vascular Surgery, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Jing-Bo
JB
Lu
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Chun-Min
CM
Kang
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Lei
L
Zheng
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Qian
Q
Wang
D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D044045:Lipoxins / Q000494:pharmacology*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D044045:Lipoxins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; C040527:lipoxin A4; D002784:Cholesterol
ABCA1; LXA4; LXRα; THP-1 macrophage-derived foam cells; cholesterol efflux