The NLRP3 inflammasome mediates liver failure by activating procaspase-1 and pro-IL-1 β and regulating downstream CD40-CD40L signaling

Li, Zenghui; Jiang, Jianning

doi:10.1177/03000605211036845

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…In contrast, hepatitis B c antigen (HBcAg) promotes LPS-induced NLRP3 inflammasome activation and IL-1β production ( Wang et al, 2019 ). At last, the counteraction turns out to be the upregulation of IL-1β found in the serum, peripheral blood mononuclear cells (PBMCs) and in vitro culture primary human hepatocytes ( Tian et al, 2019 ; Zhang Z. et al, 2020 ; Li and Jiang, 2021 ). Besides, IL-1β is also linked to IFN-α treatment response.…”

Section: Cytokines In Hepatitis B Virus Infectionmentioning

confidence: 99%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

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Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.

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Section: Cytokines In Hepatitis B Virus Infectionmentioning

confidence: 99%

Cytokines and Chemokines in HBV Infection

Zhong

Zhang

Tang

et al. 2021

Front. Mol. Biosci.

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“…HEV genotypes 3 and 4 caused increased IL-1β levels in rabbits, and HEV particles activated NLRP3 in primary macrophages and macrophage cell lines 67 . Patients with HBV-associated acute liver failure demonstrated increased expression of NLRP3 mRNA levels in their peripheral blood mononuclear cells 68 …”

Section: Concepts Of Inflammation In Chronic Liver Diseasesmentioning

confidence: 98%

“…[67] Patients with HBV-associated acute liver failure demonstrated increased expression of NLRP3 mRNA levels in their peripheral blood mononuclear cells. [68] Antagonizing NLRP3 function might appear as a potent anti-inflammatory strategy. Loss of murine NLRP3 ameliorates diet-induced steatohepatitis, whereas NLRP3 inflammasome gain of function worsens liver disease leading to severe fibrosis.…”

Section: Inflammasomes In Liver Inflammationmentioning

confidence: 99%

Therapeutic modulation of the liver immune microenvironment

2023

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Inflammation is a hallmark of progressive liver diseases such as chronic viral or immune-mediated hepatitis, alcohol-associated liver disease, and NAFLD. Preclinical and clinical studies have provided robust evidence that cytokines and related cellular stress sensors in innate and adaptive immunity orchestrate hepatic disease processes. Unresolved inflammation and liver injury result in hepatic scarring, fibrosis, and cirrhosis, which may culminate in HCC. Liver diseases are accompanied by gut dysbiosis and a bloom of pathobionts, fueling hepatic inflammation. Anti-inflammatory strategies are extensively used to treat human immune-mediated conditions beyond the liver, while evidence for immunomodulatory therapies and cell therapy–based strategies in liver diseases is only emerging. The development and establishment of novel immunomodulatory therapies for chronic liver diseases has been dampened by several clinical challenges, such as invasive monitoring of therapeutic efficacy with liver biopsy in clinical trials and risk of DILI in several studies. Such aspects prevented advancements of novel medical therapies for chronic inflammatory liver diseases. New concepts modulating the liver immune environment are studied and eagerly awaited to improve the management of chronic liver diseases in the future.

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“…For example, it has been found that the levels of NLRP3 are low in normal liver tissues; however, activation of the NLRP3 inflammasome is implicated in hepatic injury. The NLRP3 inflammasome mediates liver failure by sensitizing procaspase-1 and pro-IL-1 β in HBV-related acute-on-chronic liver failure (ACLF) ( 95 , 96 ). To date, the molecular mechanisms associated with virus-mediated sensitization of the NLRP3 inflammasome have not been well examined.…”

Section: Function Of Hbx In Nlr-mediated Signaling Pathwaysmentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.

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The NLRP3 inflammasome mediates liver failure by activating procaspase-1 and pro-IL-1 β and regulating downstream CD40-CD40L signaling

Cited by 12 publications

References 40 publications

Cytokines and Chemokines in HBV Infection

Cytokines and Chemokines in HBV Infection

Therapeutic modulation of the liver immune microenvironment

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

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