Alcohol induced NLRP3 inflammasome activation in the brain of rats is attenuated by ATRA supplementation

S, Priyanka; Thushara, A. J.; Rauf, Arun A.; Indira, M.

doi:10.1016/j.bbih.2019.100024

Cited by 7 publications

(3 citation statements)

References 38 publications

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“…In contrast, in a murine model of alcohol-induced toxicity, an in vivo study showed that ATRA induced the downregulation of NLRP3, pro-caspase-1 and pro-IL-1β mRNAs in the brain tissue, upon endotoxin treatment. This report demonstrated that while chronic alcohol exposure increased the intestinal permeability for endotoxins, and subsequently elevated the ROS level in the circulation, ATRA developed a protective effect by inhibiting these mechanisms (98).…”

Section: Retinoic Acid Receptor (Rar)mentioning

confidence: 76%

Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function

Alatshan

Benkő

2021

Front. Immunol.

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Nuclear receptors are important bridges between lipid signaling molecules and transcription responses. Beside their role in several developmental and physiological processes, many of these receptors have been shown to regulate and determine the fate of immune cells, and the outcome of immune responses under physiological and pathological conditions. While NLRP3 inflammasome is assumed as key regulator for innate and adaptive immune responses, and has been associated with various pathological events, the precise impact of the nuclear receptors on the function of inflammasome is hardly investigated. A wide variety of factors and conditions have been identified as modulators of NLRP3 inflammasome activation, and at the same time, many of the nuclear receptors are known to regulate, and interact with these factors, including cellular metabolism and various signaling pathways. Nuclear receptors are in the focus of many researches, as these receptors are easy to manipulate by lipid soluble molecules. Importantly, nuclear receptors mediate regulatory mechanisms at multiple levels: not only at transcription level, but also in the cytosol via non-genomic effects. Their importance is also reflected by the numerous approved drugs that have been developed in the past decade to specifically target nuclear receptors subtypes. Researches aiming to delineate mechanisms that regulate NLRP3 inflammasome activation draw a wide range of attention due to their unquestionable importance in infectious and sterile inflammatory conditions. In this review, we provide an overview of current reports and knowledge about NLRP3 inflammasome regulation from the perspective of nuclear receptors, in order to bring new insight to the potentially therapeutic aspect in targeting NLRP3 inflammasome and NLRP3 inflammasome-associated diseases.

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Section: Retinoic Acid Receptor (Rar)mentioning

confidence: 76%

Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function

Alatshan

Benkő

2021

Front. Immunol.

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“…As the alcohol induced neuroinflammation in the brain, the IL-1β level increased through the activation of the NLRP3 inflammasome [ 66 ]. Our results demonstrated a pivotal role for NLRP3 inflammasome activation that mediates the IL-1β level in the alcohol-related neuroinflammation.…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

et al. 2022

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Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

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“…All these inflammatory mechanisms are enhanced by alcohol consumption. Ethanol has been reported to independently cause hyperactivation of STAT3, IKBα, and NLRP3 inflammasome both in vitro and in vivo [ 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%