期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 29, 期 14, 页码 2153-2171出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v29.i14.2153
关键词
Hepatic alveolar echinococcosis; Inflammasome; Inflammation; Kupffer cell; NLR family pyrin domain-containing 3 protein; Reactive oxygen species
This study investigated the role and activation mechanism of the NLRP3 inflammasome in hepatic alveolar echinococcosis (HAE). The results showed that the activation of the inflammasome is associated with reactive oxygen species (ROS), and inhibition of ROS production can decrease the activation of the NLRP3-caspase-1-IL-1 beta pathway, thereby mitigating hepatocyte damage and inflammation.
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)-1 beta, 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-1 beta, 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-1 beta 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-1 beta pathway in Kupffer cells, indicating that ROS may serve as a potential target for the treatment of HAE.
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