Deubiquitinase Inhibitor b-AP15 Attenuated LPS-Induced Inflammation via Inhibiting ERK1/2, JNK, and NF-Kappa B

• Published in: Frontiers in molecular biosciences Vol. 7; p. 49
• Main Authors: Zhang, Fangcheng, Xu, Ruqin, Chai, Renjie, Xu, Qiong, Liu, Mingke, Chen, Xuke, Chen, Xiaohua, Kong, Tianyu, Zhang, Chongyu, Liu, Shi-Ming, Zhang, Zhenhui, Liu, Ningning
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.04.2020
• Subjects: b-AP15; deubiquitinase inhibitor; ERK1/2; inflammation; JNK; Molecular Biosciences; NF-κB; NF-κB; ERK1/2; deubiquitinase inhibitor; inflammation; b-AP15; JNK
• ISSN: 2296-889X; 2296-889X
• DOI: 10.3389/fmolb.2020.00049

b-AP15 is a deubiquitinase (DUB) inhibitor of 19S proteasomes, which in turn targets ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14). Nuclear factor kappa B (NF-κB) is closely linked to cellular response in macrophages when the organism is in the state of microbial infection, and it acts as a vital part in the mechanism of inflammatory reaction. However, the molecular mechanism by which DUB inhibitors, especially b-AP15, regulates inflammation remains poorly understood. This study aimed to investigate the relationship between b-AP15 and inflammation. The results showed that b-AP15 treatment significantly reduced the amounts of inflammatory indicators, such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated THP-1 and macrophages. Meanwhile, similar results were obtained from experiments. In addition, b-AP15 also significantly improved the survival rate of sepsis mouse via high-density LPS mediation. Furthermore, b-AP15 also inhibited the ERK1/2 and JNK phosphorylation, increased IκBα levels, and inhibited NF-κB p65 by removing them from the cytoplasm into the nucleus. All these findings suggested that b-AP15 has anti-inflammatory action and acts as a potential neoteric target drug for treating microbial infection.