Transcriptional enhancement of GBP‐5 by BATF aggravates sepsis‐associated liver injury via NLRP3 inflammasome activation

Autor: Hong-Li Guo, Jing Xu, Zhaoying Yao, Ming-Ming Ni, Yiqin Yao, Chao Liu, Feng Chen, Qianming Du
Rok vydání: 2021
Předmět:
Zdroj: The FASEB Journal. 35
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.202100234r
Popis: Strong inflammatory response triggered by the activation of the innate immune system is one typical characteristic of sepsis-associated liver injury (SALI). Guanylate-binding protein 5 (GBP-5) is a component of cell-autonomous immunity and known to be associated with inflammation. Currently, whether GBP-5 participates in SALI and its roles in this disease are yet to be investigated. Using a lipopolysaccharide (LPS)-induced SALI mouse model, we found GBP-5 was highly expressed in LPS-treated mice, and its expression was tightly related to the serum concentrations of live injury markers and inflammatory cytokines, liver damage scores by H&E staining, and amounts of apoptotic hepatocytes by TUNEL staining. Moreover, GBP-5 overexpression was found to aggravate LPS-induced SALI by promoting the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome, then facilitated the production of pro-inflammatory cytokines, eventually induced hepatocyte cell death. Direct transcriptional activation of GBP-5 by basic leucine zipper ATF-like transcription factor (BATF) was identified and further validated. This study unveils a transcriptional upregulation of GBP-5 by interacting with BATF, which promotes the progression of LPS-induced SALI through NLRP3 inflammasome activation, and provides novel therapeutic insights for halting the progression of liver injury in various liver diseases.
Databáze: OpenAIRE
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