The Impact of the NLRP3 Pathway in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Alcohol-Related Liver Disease

Sheriff, Lozan

doi:10.3390/livers1020007

Cited by 4 publications

(3 citation statements)

References 96 publications

(133 reference statements)

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“…In experimental as well as clinical scenarios in humans, alcoholic liver injury is closely associated with inflammasome activation [63]. Alcohol is metabolized primarily in the liver, and this metabolism generates acetaldehyde and ROS, both of which are highly toxic compounds.…”

Section: Alcohol-induced Hepatotoxicitymentioning

confidence: 99%

Mechanisms of Inflammasome Activation and Involvement in Liver Disease

Baral

2024

JMP

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The liver is a multi-potent organ with important metabolic, immunological and endocrine functions. Hepatic physiology is maintained at a balanced state via the delicate actions of different liver-resident cells. Among several factors that modulate hepatic physiology, the harmony between the activity of pro- and anti-inflammatory cytokines is a crucial determinant. However, initiation of inflammatory activity can be detrimental if it goes unresolved, leading to severe consequences such as hepatitis, hepatic fibrosis, cirrhosis or even hepatocellular carcinoma (HCC). Different physiological processes can modulate the hepatic microenvironment; one such factor is a cytosolic protein complex called the inflammasome. Inflammasome activation is a consequence of the cellular encounter with pathogens or products of cellular damage. Once activated, inflammasomes promote the maturation of interleukin-1 family cytokines such as IL-1β and IL-18 via activation of caspase-1. These cytokines have a very potent role in modulating hepatic physiology. Various lines of reports suggest that inflammasome activation and IL-1 cytokines play critical roles in liver diseases, including hepatitis, hepatic fibrosis and HCC. Conversely, inhibition of inflammasome activation and/or IL-1 signaling prevents such effects. This review summarizes the mechanisms leading to inflammasome activation and the role it plays in hepatic physiology.

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Section: Alcohol-induced Hepatotoxicitymentioning

confidence: 99%

Mechanisms of Inflammasome Activation and Involvement in Liver Disease

Baral

2024

JMP

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“…Further, pyroptosis-produced cytokines and chemokines bind to their cognate receptors on the immune cells like leukocytes and lymphocytes to activate the signal transduction pathways such as NF-κB and MAPK that enhance pro-inflammatory cytokines such as TNF-α, IL-6, and IL-17 as well as chemokines to induce the inflammatory response ( 32 – 34 ). Aberrant activation of the NLRP3 inflammasome-mediated release of pro-inflammatory cytokines from hepatocytes recruits peripheral mononuclear cells to the microenvironment and promotes inflammation and tissue damage ( 35 ). As suggested, inflammasomes exist in parenchymal and non-parenchymal cells of liver and are emerging as pathogenic mediators in ALD as well as non-alcoholic fatty liver disease.…”

Section: Role Of Nlrp3 Inflammasomes In Normal Physiological Conditionmentioning

confidence: 99%

NLRP3: a new therapeutic target in alcoholic liver disease

et al. 2023

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The liver is in charge of a wide range of critical physiological processes and it plays an important role in activating the innate immune system which elicits the inflammatory events. Chronic ethanol exposure disrupts hepatic inflammatory mechanism and leads to the release of proinflammatory mediators such as chemokines, cytokines and activation of inflammasomes. The mechanism of liver fibrosis/cirrhosis involve activation of NLRP3 inflammasome, leading to the destruction of hepatocytes and subsequent metabolic dysregulation in humans. In addition, increasing evidence suggests that alcohol intake significantly modifies liver epigenetics, promoting the development of alcoholic liver disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, and DNA methylation are crucial in alcohol-evoked cell signaling that affects gene expression in the hepatic system. Though we are at the beginning stage without having the entire print of epigenetic signature, it is time to focus more on NLRP3 inflammasome and epigenetic modifications. Here we review the novel aspect of ALD pathology linking to inflammation and highlighting the role of epigenetic modification associated with NLRP3 inflammasome and how it could be a therapeutic target in ALD.

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“… 30 Animal models of AIH demonstrate increased expression of NLRP3 inflammasome in the blood 32 ; similar observations have been made in mice models of MASLD, with NLRP3 activation driving fibrosis and progression to metabolic-associated steatohepatitis. 33 Further, the NLRP3 inflammasome has been implicated in MASLD progression, with studies reporting a higher level of NLRP3 components in patients with metabolic-associated steatohepatitis compared with those without metabolic-associated steatohepatitis. 34 …”

Section: Introductionmentioning

confidence: 99%

Autoimmune hepatitis: Current and future therapies

Reau,

Lammert,

Weinberg

2024

Hepatology Communications

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Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.

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The Impact of the NLRP3 Pathway in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Alcohol-Related Liver Disease

Cited by 4 publications

References 96 publications

Mechanisms of Inflammasome Activation and Involvement in Liver Disease

Mechanisms of Inflammasome Activation and Involvement in Liver Disease

NLRP3: a new therapeutic target in alcoholic liver disease

Autoimmune hepatitis: Current and future therapies

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