Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating Jmjd3.
作者：
Salloum, Zeina;Dauner, Kristin;Li, Yun-Feng;Verma, Neha*;Valdivieso-González, David;...
通讯作者：
Verma, Neha
作者机构：
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Canada
Wuhan University, Wuhan, China
2015202040152@whu.edu.cn, Ottawa Hospital Research Institute, Ottawa, Canada
3Departamento Química Física, Universidad Complutense de Madrid, Madrid, Spain
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada
Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, United States
Departamento Química Física, Universidad Complutense de Madrid, Madrid, Spain
通讯机构：
Ottawa Hospital Research Institute, Ottawa, Canada
语种：
英文
关键词：
cell biology,mouse
期刊：
ELIFE
ISSN：
2050-084X
年：
2024
卷：
13
摘要：
Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1),...
