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Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression.

ABSTRACT: BACKGROUND:Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established. RESULTS:This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-?B pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection. CONCLUSIONS:These results indicate that during Sj infection tTG may control liver fibrosis at least partially through TLR4, NF-?B pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj infection.

SUBMITTER: Li ZY

PROVIDER: S-EPMC6570881 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression.

Li Zhi-Yong ZY Xiao LinZhuo L Lin GuiYing G Tang JuanJuan J Chen YuQiang Y Chen Lan L Li BaoQi B Wu MeiLing M Liu ShuYan S Huang ChuQin C Ferrandon Dominique D Li Zi Z

Parasites & vectors 20190614 1

<h4>Background</h4>Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established.<h4>Results</h4>Thi ...[more]

PMID: 31200771

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Project description:Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis.

Dataset Information

Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression.

Publications

Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression.

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