Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux
Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux
复制标题
抑制 NLRP3 炎症小体可通过抑制 ox-LDL 摄取和促进胆固醇流出来减弱 THP-1 巨噬细胞泡沫细胞的形成
DOI：
10.1016/j.bbrc.2017.11.025
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Qu, Peng
中科院分区：
文献类型：
--
作者：
Chen, Liang;Yao, Qiying;Qu, Peng
NLRP3是NOD样受体家族，在动脉粥样硬化的发生发展过程中起着重要的作用。激活的NLRP3炎性小体已被报道促进巨噬细胞泡沫细胞的形成，但并不是所有的研究都获得了相同的结果，NLRP3炎性小体如何参与泡沫细胞的形成仍不清楚。我们使用选择性的NLRP3炎性小体抑制剂和NLRP3缺失的THP-1细胞来评估NLRP3炎性小体抑制对巨噬细胞泡沫细胞形成、氧化低密度脂蛋白(ox-LDL)摄取、酯化和胆固醇流出以及相关蛋白表达的影响。抑制NLRP3炎性小体可以减少泡沫细胞的形成，减少OX-LDL的摄取，并促进THP-1巨噬细胞的胆固醇外流。下调CD36、酰基辅酶A：胆固醇酰基转移酶-1和中性胆固醇酯水解酶的表达，上调ATP结合盒转运体A1(ABCA1)和清道夫受体BI型(SR-BI)的表达，但对清道夫受体A类和ATP结合盒转运体G1的表达无影响。总之，我们的研究结果表明，抑制NLRP3炎症小体通过抑制ox-LDL摄取和促进胆固醇流出减少THP-1巨噬细胞的泡沫细胞形成，这可能分别是由于CD36表达下调和ABCA1和SR-BI表达上调所致。(C)2017 Elsevier Inc.保留所有权利。
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 Gl. 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. (C) 2017 Elsevier Inc. All rights reserved.