Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.11.025· OSTI ID:23100623

Chen, Liang ^[1]; Yao, Qiying ^[2]; Xu, Siwei; Wang, Hongyan; Qu, Peng ^[1]

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1. Department of Cardiology, Institute of Heart and Vascular Diseases, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning (China)
2. Department of Physiology, School of Basic Medical Science, Dalian Medical University, Dalian, Liaoning (China)

Highlights: • NLRP3 inflammasome inhibition attenuates foam cell formation of THP-1 macrophages. • NLRP3 inflammasome inhibition diminishes ox-LDL uptake in THP-1 macrophages. • NLRP3 inflammasome inhibition promotes cholesterol efflux from THP-1 macrophages. • NLRP3 inflammasome inhibition downregulates CD36 expression. • NLRP3 inflammasome inhibition upregulates ABCA1 and SR-BI expression. The NOD-like receptor family, pyrin domain–containing protein 3 (NLRP3) inflammasome plays an important role in the development of atherosclerosis. The activated NLRP3 inflammasome has been reported to promote macrophage foam cell formation, but not all studies have obtained the same result, and how NLRP3 inflammasome is involved in the formation of foam cells remains elusive. We used selective NLRP3 inflammasome inhibitors and NLRP3-deficient THP-1 cells to assess the effect of NLRP3 inflammasome inhibition on macrophage foam cell formation, oxidized low-density lipoprotein (ox-LDL) uptake, esterification, and cholesterol efflux, as well as the expression of associated proteins. Inhibition of the NLRP3 inflammasome attenuated foam cell formation, diminished ox-LDL uptake, and promoted cholesterol efflux from THP-1 macrophages. Moreover, it downregulated CD36, acyl coenzyme A: cholesterol acyltransferase-1 and neutral cholesterol ester hydrolase expression; upregulated ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression; but had no effect on the expression of scavenger receptor class A and ATP-binding cassette transporter G1. Collectively, our findings show that inhibition of the NLRP3 inflammasome decreases foam cell formation of THP-1 macrophages via suppression of ox-LDL uptake and enhancement of cholesterol efflux, which may be due to downregulation of CD36 expression and upregulation of ABCA1 and SR-BI expression, respectively.

• OSTI ID: 23100623
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARTERIOSCLEROSIS
CHOLESTEROL
COENZYMES
HYDROLASES
LIPOPROTEINS
MACROPHAGES