HDAC7 Activates IKK/NF-κB Signaling to Regulate Astrocyte-Mediated Inflammation

Autor: Jinwang Ye, Suyue Zhong, Yunsong Deng, Xuanbao Yao, Qiong Liu, Jian-Zhi Wang, Shifeng Xiao
Rok vydání: 2022
Předmět:
Zdroj: Molecular Neurobiology. 59:6141-6157
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-022-02965-6
Popis: 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.
Databáze: OpenAIRE
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