炎症体
HDAC11型
基因敲除
目标2
细胞生物学
HDAC4型
吡喃结构域
生物
组蛋白脱乙酰基酶
下调和上调
癌症研究
分子生物学
炎症
化学
免疫学
细胞培养
组蛋白
生物化学
基因
遗传学
作者
Hye-Eun Byeon,Sung‐E Choi,Yujin Kim,Suji Choi,Soojin Lee,Hyoung‐Il Kim,Jung‐Soon Mo,Ja Young Jeon
出处
期刊:Endocrinology
[The Endocrine Society]
日期:2024-01-16
卷期号:165 (3)
被引量:1
标识
DOI:10.1210/endocr/bqae011
摘要
Abstract Histone deacetylase 11 (HDAC11) has been implicated in the pathogenesis of metabolic diseases characterized by chronic low-grade inflammation, such as obesity. However, the influence of HDAC11 on inflammation and the specific effect of HDAC11 on the palmitic acid (PA)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation are poorly understood. The effect of PA treatment on HDAC11 activity and the NLRP3 inflammasome was investigated in human peripheral blood mononuclear cells and THP-1 cells. The PA-induced responses of key markers of NLRP3 inflammasome activation, including NLRP3 gene expression, caspase-1 p10 activation, cleaved IL-1β production, and extracellular IL-1β release, were assessed as well. The role of HDAC11 was explored using a specific inhibitor of HDAC11 and by knockdown using small interfering (si)HDAC11 RNA. The relationship between HDAC11 and yes-associated protein (YAP) in the PA-induced NLRP3 inflammasome was investigated in THP-1 cells with HDAC11 or YAP knockdown. Following PA treatment, HDAC11 activity and protein levels increased significantly, concomitant with activation of the NLRP3 inflammasome. Notably, PA-induced the upregulation of NLRP3, caspase-1 p10 activation, the production of cleaved IL-1β, and the release of IL-1β into the extracellular space, all of which were attenuated by FT895 treatment and by HDAC11 knockdown. In THP-1 cells, PA induced the expression of YAP and its interaction with NLRP3, resulting in NLRP3 inflammasome activation, whereas both were inhibited by FT895 and siHDAC11 RNA. These findings demonstrate a pivotal role for HDAC11 in the PA-induced activation of the NLRP3 inflammasome. HDAC11 inhibition thus represents a promising therapeutic strategy for mitigating NLRP3 inflammasome-related inflammation in the context of obesity.
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