1. Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis
- Author
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Rong Fu, Shi-Jia Zu, Yan-Jun Liu, Jia-Cheng Li, Wen-Zhen Dang, Li-Ping Liao, Li-Ping Liu, Pan-Yu Chen, He-Ming Huang, Kang-Hui Wu, Bing Zhou, Qin Pan, Cheng Luo, Yuan-Yuan Zhang, and Guang-Ming Li
- Subjects
Inflammation ,Liver Cirrhosis ,Macrophages ,Hepatic Stellate Cells ,Cytokines ,Humans ,Bioengineering ,General Medicine ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
Liver fibrosis occurs following inflammation triggered by the integrated actions of activated liver-resident macrophages (Kupffer cells) and hepatic stellate cells (HSCs), and the multiplicity of these mechanisms complicates drug therapy. Here, we demonstrate that the selective bromodomain and extra-terminal (BET) bromodomain inhibitor compound38 can block both the Janus kinase-signal transducer and activator of transcription and mitogen-activated protein kinase signaling pathways in macrophages, which decreased their secretion of proinflammatory cytokines in a dose-dependent manner. The inactivation of macrophages attenuated lipopolysaccharide-induced injurious inflammation concurrent with a reduction in F4/80+ cells, proinflammatory cytokine levels, and neutrophil infiltration. Moreover, compound 38 inhibited the Wnt/β-catenin and transforming growth factor-beta/SMAD signaling pathways to abolish the activation of HSCs.
- Published
- 2022