Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation

Autor: Zhixin Chen, Xiao-Xia Xie, Wen-Hui Xie, Xiao-Huang Yang, Jian Ding, Wen-Yu Gao, Qi-Lan Guo, Xiao-Fan Wu, Dan Li, Xiao-Zhong Wang
Rok vydání: 2020
Předmět:
0301 basic medicine
Hepatitis B virus
Carcinoma
Hepatocellular
Inflammasomes
Immunology
Gene Expression
Mitochondria
Liver
Inflammation
Mitochondrion
Transfection
HMGB1
Cell Line
Liver inflammation
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
NLR Family
Pyrin Domain-Containing 3 Protein
Pyroptosis
medicine
Humans
Viral Regulatory and Accessory Proteins
Propidium iodide
Pharmacology
integumentary system
biology
Liver cell
Liver Neoplasms
Inflammasome
Hydrogen Peroxide
Molecular biology
digestive system diseases
NLRP3 inflammasome
Hepatitis B virus X protein
CARD Signaling Adaptor Proteins
Original Research Paper
Oxidative Stress
HBx
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
DNA
Viral
Hepatocytes
Trans-Activators
biology.protein
medicine.symptom
Reactive Oxygen Species
medicine.drug
Zdroj: Inflammation Research
ISSN: 1420-908X
1023-3830
Popis: Objective Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis under oxidative stress. Methods The effect of HBx on the NLRP3 inflammasome was analyzed by enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence in hepatic HL7702 cells. Pyroptosis was evaluated by western blotting, lactate dehydrogenase release, propidium iodide staining, and transmission electron microscopy. NLRP3 expression in the inflammasome from liver tissues was assessed by immunohistochemistry. Results In hydrogen peroxide (H2O2)-stimulated HL7702 cells, HBx triggered the release of pro-inflammatory mediators apoptosis-associated speck-like protein containing a CARD (ASC), interleukin (IL)-1β, IL-18, and high-mobility group box 1 (HMGB1); activated NLRP3; and initiated pro-inflammatory cell death (pyroptosis). HBx localized to the mitochondria, where it induced mitochondrial damage and production of mitochondrial reactive oxygen species (mitoROS). Treatment of HL7702 cells with a mitoROS scavenger attenuated HBx-induced NLRP3 activation and pyroptosis. Expression levels of NLRP3, ASC, and IL-1β in liver tissues from patients were positively correlated with HBV DNA concentration. Conclusions The NLRP3 inflammasome was activated by elevated mitoROS levels and mediated HBx-induced liver inflammation and hepatocellular pyroptosis under H2O2-stress conditions.
Databáze: OpenAIRE
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