Taurine Alleviates Schistosoma-Induced Liver Injury by Inhibiting the TXNIP/NLRP3 Inflammasome Signal Pathway and Pyroptosis

Liu, Xin; Zhang, Ya-Rong; Cai, Chen; Ni, Xian-Qiang; Zhu, Qing; Ren, Jianjun; Chen, Yao; Zhang, Lin-Shuang; Xue, Chang-Ding; Zhao, Jie; Qi, Yongfen; Yu, Yan-Rong

doi:10.1128/iai.00732-19

Cited by 47 publications

(35 citation statements)

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“…Inflammation plays an important role in the development and progression of liver fibrosis [36,37]. Previously, S. mansoni infection has been shown to activates NLRP3 inflammasomes in vitro and in vivo models [4][5][6]. Since Sch B has been shown to ameliorates inflammasome activation in various inflammatory models [27][28][29]33], to also verify the protective effects of Sch B against S. mansoni-induced liver fibrosis, we examined the effects of Sch B on the NLRP3 inflammasome pathway.…”

Section: Schisandrin B Reduces S Mansoni-induced Inflammation Through Inhibition Of Inflammasomementioning

confidence: 99%

“…Inflammasomes have been found to regulate important aspects of tissue inflammation. The activation of NOD-like receptor family pyrin domain-containing three (NLRP3) inflammasomes has been shown during Schistosoma-infected liver fibrosis [4][5][6]. Once NLRP3 is activated, it recruits an adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and induces activation of caspase-1.…”

Section: Introductionmentioning

confidence: 99%

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Ameliorative effects of Schisandrin B on Schistosoma mansoni-induced hepatic fibrosis in vivo

2021

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Schistosomiasis is second only to malaria as the most devastating parasitic disease in the world. It is caused by the helminths Schistosoma mansoni (S. mansoni), S. haematobium, or S. japonicum. Typically, patients with schistosomiasis suffer from symptoms of liver fibrosis and hepatosplenomegaly. Currently, patients were treated with praziquantel. Although praziquantel effectively kills the worm, it cannot prevent re-infection or resolve liver fibrosis. Also, current treatment options are not ample to completely cure liver fibrosis and splenic damages. Moreover, resistance of praziquantel has been reported in vivo and in vitro studies. Therefore, finding new effective treatment agents is urgently needed. Schisandrin B (Sch B) of Schisandra chinensis has been shown to protect against different liver injuries including fatty liver disease, hepatotoxicity, fibrosis, and hepatoma. We herein investigate the potential of using Sch B to treat S. mansoni-induced liver fibrosis. Results from the present study demonstrate that Sch B is beneficial in treating S. mansoni-induced liver fibrosis and splenic damages, through inhibition of inflammasome activation and apoptosis; and aside from that regulates host immune responses. Besides, Sch B treatment damages male adult worm in the mice, consequently helps to reduce egg production and lessen the parasite burden.

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Section: Schisandrin B Reduces S Mansoni-induced Inflammation Through Inhibition Of Inflammasomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ameliorative effects of Schisandrin B on Schistosoma mansoni-induced hepatic fibrosis in vivo

2021

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“…During human NAFLD/NASH, GSDMD and its N-terminal peptide (GSDMD-N) are upregulated, besides MCD-fed Gsdmd −/− mice showed decreased severity of steatosis and inflammation comparing to WT (52). During Schistosoma infection, Liu and colleagues (2019) demonstrated that S. japonicum induces expression of the GSDMD-N in the liver, and that this expression is modulated by NLRP3 sensor (53). In addition, it has been reported that SEA from S. japonicum eggs induces pyroptosis in HSCs (54).…”

Section: Discussionmentioning

confidence: 99%

NLRP6 Plays an Important Role in Early Hepatic Immunopathology Caused by Schistosoma mansoni Infection

et al. 2020

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Schistosomiasis is a debilitating parasitic disease that affects more than 200 million people worldwide and causes approximately 280,000 deaths per year. Inside the definitive host, eggs released by Schistosoma mansoni lodge in the intestine and especially in the liver where they induce a granulomatous inflammatory process, which can lead to fibrosis. The molecular mechanisms initiating or promoting hepatic granuloma formation remain poorly understood. Inflammasome activation has been described as an important pathway to induce pathology mediated by NLRP3 receptor. Recently, other components of the inflammasome pathway, such as NLRP6, have been related to liver diseases and fibrotic processes. Nevertheless, the contribution of these components in schistosomiasis-associated pathology is still unknown. In the present study, using dendritic cells, we demonstrated that NLRP6 sensor is important for IL-1β production and caspase-1 activation in response to soluble egg antigens (SEA). Furthermore, the lack of NLRP6 has been shown to significantly reduce periovular inflammation, collagen deposition in hepatic granulomas and mRNA levels of α-SMA and IL-13. Livers of Nlrp6 −/− mice showed reduced levels of CXCL1/KC, CCL2, CCL3, IL-5, and IL-10 as well as Myeloperoxidase (MPO) and Eosinophilic Peroxidase (EPO) enzymatic activity. Consistently, the frequency of macrophage and neutrophil populations were lower in the liver of NLRP6 knockout mice, after 6 weeks of infection. Finally, it was further demonstrated that the onset of hepatic granuloma and collagen deposition were also compromised in Caspase-1 −/− , IL-1R −/− and Gsdmd −/− mice. Our findings suggest that the NLRP6 inflammasome is an important component for schistosomiasis-associated pathology.

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“…Increasing evidences show that in ammatory processes are crucial for the pathogenesis and progression of serious liver diseases [10,13,15] . NLRP3 in ammasome has signi cant role in the innate immune system involving the in ammatory response [17,24] . Here, we nd that the expression of NLRP3, Caspase-1, and IL-1β in the in ammatory marginal zone of HAE patients are signi cantly increased.…”

Section: Discussionmentioning

confidence: 99%

“…The NLRP3 in ammasome is an important participant in in ammatory responses and has been closely associated with in ammation in various liver diseases, including liver cancer (Wei 2014, Saber 2010, Wei 2019) [10][11][12] , viral hepatitis (Ding 2019, McRae 2016) [13,14] , non-alcoholic fatty liver (Sun 2020, Dwivedi 2020) [15,16], and schistosomiasis (Liu 2019, Chen 2019) [17,18] . However, the role and clinical signi cance of the NLRP3 in ammasome in HAE remain unclear.…”

Section: Introductionmentioning

confidence: 99%

The Effect and Mechanism of ROS-Mediated Activation of NLRP3 Inflammasome in Hepatic Alveolar Echinococcosis

chen

zhang²,

wang

et al. 2020

Preprint

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Background: The 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. Therefore, we aimed to investigate the NLRP3 inflammasome and its activation mechanism in HAE.Method: We assessed the expression of NLRP3, Caspase-1, interleukin (IL)-1β, and IL-18 in the inflammatory marginal zone and corresponding normal liver tissues of 60 patients with HAE. We used a rat model of HAE to investigate the role of the NLRP3 inflammasome in the inflammatory marginal zone of HAE. Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis in stimulating Kupffer cells and hepatocytes. Further, immunohistochemical staining, western blotting, and ELISA assessed the expression of NLRP3 and Caspase-1, IL-1β, and IL-18, and flow cytometry was used to detect apoptosis and ROS.Results: The activation of NLRP3 inflammasome was intimately associated with the expression of ROS(P<0.05). Inhibition of ROS generation decreased the activation of NLRP3-Caspase-1-IL-1β pathway and mitigated damage to hepatocytes (P <0.01) as well as inflammation (P <0.001) in HAEConclusion: E. multilocularis can induce hepatocytes damage and inflammatory response by activating the ROS-NLRP3-Caspase-1-IL-1β pathway in Kupffer cells, indicating that ROS may be a potential target for the treatment of HAE.

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Taurine Alleviates Schistosoma-Induced Liver Injury by Inhibiting the TXNIP/NLRP3 Inflammasome Signal Pathway and Pyroptosis

Cited by 47 publications

References 46 publications

Ameliorative effects of Schisandrin B on Schistosoma mansoni-induced hepatic fibrosis in vivo

Ameliorative effects of Schisandrin B on Schistosoma mansoni-induced hepatic fibrosis in vivo

NLRP6 Plays an Important Role in Early Hepatic Immunopathology Caused by Schistosoma mansoni Infection

The Effect and Mechanism of ROS-Mediated Activation of NLRP3 Inflammasome in Hepatic Alveolar Echinococcosis

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