Research Paper|Volume 12, Issue 2|pp 1747—1759

K63 ubiquitin chains target NLRP3 inflammasome for autophagic degradation in ox-LDL-stimulated THP-1 macrophages

Zhenfeng Zhou¹, Xiaoyan Zhu², Ruihua Yin¹, Tianwei Liu³, Shaonan Yang¹, Lingyan Zhou¹, Xudong Pan^1,³, Aijun Ma^1,³

¹Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
²Department of Intensive Care Unit, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
³Institute of Cerebrovascular Diseases, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China

* Equal contribution

Received: August 23, 2019Accepted: January 2, 2020Published: January 29, 2020

Copyright: © 2020 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Inflammation, especially involving the NLRP3 inflammasome, is critical to atherosclerotic plaque formation. Enhanced autophagy can inhibit the development of atherosclerosis, and recent studies have revealed that NLRP3 inflammasome can be degraded by autophagy in atherosclerosis. In the present study, we established a foam-cell model to investigate the impact of oxidized low density lipoproteins (ox-LDLs) on autophagy and the inflammasome in atherosclerosis-related inflammation. We observed that ox-LDLs activated NLRP3 inflammasomes in macrophages and restricted autophagy in a time-and dose-dependent manner. We further observed through immunoprecipitation and siRNA knockdown that autophagic degradation of the NLRP3 inflammasome is dependent on K63 polyubiquitation of its NLRP3 subunit and subsequent binding by the adaptor protein p62. Our findings uncover a mechanism by which autophagy inhibits inflammation in atherosclerosis and the role of K63 in that process.