HDAC7 Activates IKK/NF-κB Signaling to Regulate Astrocyte-Mediated Inflammation.
|
| Abstract |
Class IIa histone deacetylases (HDAC) have been shown to drive innate immune cell-mediated inflammation in the peripheral system, but their roles in cerebral inflammatory responses remain largely unknown. Here, we elucidate that HDAC7 is selectively elevated in lipopolysaccharide (LPS)-challenged astrocytes both in vivo and in vitro. We identify that HDAC7 binds to the inhibitory kappa B kinase (IKK) to promote IKKα and IKKβ deacetylation and subsequent activation, leading to the activation of nuclear factor κB (NF-κB). Astrocyte-specific overexpression of HDAC7 results in NF-κB activation, pro-inflammatory gene upregulation and anxiety-like behaviors in mice, while downregulating HDAC7 reserves LPS-induced NF-κB activation and inflammatory responses. Furthermore, pharmacological inhibition of HDAC7 by a class IIa HDAC inhibitor attenuates LPS-induced NF-κB activation, inflammatory responses and anxiety-like behaviors both in vivo and in vitro. Together, our data reveal a novel mechanism of HDAC7 in astrocyte-mediated inflammation and suggest that targeting HDAC7 could be a potential therapeutic strategy for the treatment of anxiety and other inflammation-related diseases.
|
|---|---|
| Authors | Jinwang Ye, Suyue Zhong, Yunsong Deng, Xuanbao Yao, Qiong Liu, Jian-Zhi Wang, Shifeng Xiao |
| Journal | Molecular neurobiology (Mol Neurobiol) Vol. 59 Issue 10 Pg. 6141-6157 (Oct 2022) ISSN: 1559-1182 [Electronic] United States |
| PMID | 35871708 (Publication Type: Journal Article) |
| Copyright | © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!