Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2023; 29(14): 2153-2171
Published online Apr 14, 2023. doi: 10.3748/wjg.v29.i14.2153
Effect and mechanism of reactive oxygen species-mediated NOD-like receptor family pyrin domain-containing 3 inflammasome activation in hepatic alveolar echinococcosis
Cai-Song Chen, Yao-Gang Zhang, Hai-Jiu Wang, Hai-Ning Fan
Cai-Song Chen, Research Center for High Altitude Medicine of Qinghai University, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
Yao-Gang Zhang, Hai-Jiu Wang, Qinghai Province Research Key Laboratory for Echinococcosis, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
Hai-Ning Fan, Department of Hepatobiliary and Pancreatic Surgery, Qinghai Province Research Key Laboratory for Echinococcosis, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China
Author contributions: Chen CS and Fan HN conceived and designed the experiments; Chen CS, Zhang YG, and Wang HJ collected the samples; Chen CS and Zhang YG performed the experiments and data analyses; Chen CS wrote the first draft of the manuscript; Zhang YG and Fan HN provided comments for the revisions; all authors read and approved the final manuscript.
Supported by the National Major Research and Development Project of “Precision Medicine Research”, No. 2017YFC0909900; Qinghai Province Science and Technology Department Programme, No. 2019-SF-131; and the Qinghai Province Health and Family Planning Commission Programme, No. 2016-wjzd-04.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Affiliated Hospital of Qinghai University (approval No. P-SL-2019054).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of the Affiliated Hospital of Qinghai University (approval No. 2019-SF-131).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Ning Fan, MD, Doctor, Professor, Department of Hepatobiliary and Pancreatic Surgery, Qinghai Province Research Key Laboratory for Echinococcosis, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, Xining 810001, Qinghai Province, China. fanhaining6@yeah.net
Received: December 17, 2022
Peer-review started: December 17, 2022
First decision: January 22, 2023
Revised: February 1, 2023
Accepted: March 15, 2023
Article in press: March 15, 2023
Published online: April 14, 2023
Processing time: 116 Days and 18.6 Hours
Abstract
BACKGROUND

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases. However, its role in hepatic alveolar echinococcosis (HAE) remains unclear.

AIM

To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.

METHODS

We assessed the expression of NLRP3, caspase-1, interleukin (IL)-1β, and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE. A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE. Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis (E. multilocularis) in stimulating Kupffer cells and hepatocytes. Furthermore, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay were used to evaluate NLRP3, caspase-1, IL-1β, and IL-18 expression; flow cytometry was used to detect apoptosis and reactive oxygen species (ROS).

RESULTS

NLRP3 inflammasome activation was significantly associated with ROS. Inhibition of ROS production decreased NLRP3-caspase-1-IL-1β pathway activation and mitigated hepatocyte damage and inflammation.

CONCLUSION

E. multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1β pathway in Kupffer cells, indicating that ROS may serve as a potential target for the treatment of HAE.

Keywords: Hepatic alveolar echinococcosis; Inflammasome; Inflammation; Kupffer cell; NLR family pyrin domain-containing 3 protein; Reactive oxygen species

Core Tip: In recent years, the role of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in parasitic diseases has attracted widespread attention. However, the role and clinical significance of the NLRP3 inflammasome in Hepatic alveolar echinococcosis (HAE) remain unclear. Herein, we explored the mode of NLRP3 inflammasome activation in the tissues of patients with HAE, a rat model of HAE, rat Kupffer cells, and hepatocytes. Our experiments showed that inhibiting reactive oxygen species (ROS) production reduces NLRP3-caspase-1-IL-1β pathway activation. Decreased IL-1β expression alleviated inflammation and apoptosis rates in hepatocytes in HAE. We conclude that ROS-mediated NLRP3 inflammasome activation was a key factor leading to hepatocyte injury and triggering a cascade of inflammatory reactions. Therefore, ROS production may be a promising target for the treatment of HAE.