NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

Wei, Shanshan; Ma, Wanjun; Zhang, Bikui; Li, Wenqun

doi:10.3389/fcell.2021.634607

Cited by 24 publications

(16 citation statements)

References 206 publications

(253 reference statements)

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“…60, NO. 1 (21)(22)(23). Here, we reported that NLRP3 inflammasome was activated in LPS-treated HK2 cells, which was consistent with previous studies (24,25).…”

Section: Discussionsupporting

confidence: 91%

Circ_0001818 Targets Mir-136-5p to Increase Lipopolysaccharide-Induced Hk2 Cell Injuries by Activating Txnip/Nlrp3 Inflammasome Pathway

Feng

Wang

You

et al. 2023

Shock

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Background: The implication of circular RNAs (circRNAs) in sepsis-related complications arouses much attention, which provides additional treatment options for sepsis-related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods: Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818, miR-136-5p, and thioredoxin interacting protein (TXNIP) mRNA were examined by quantitative real-time polymerase chain reaction. Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic curve was depicted to assess the diagnostic value of circ_0001818, miR-136-5p, and TXNIP in serumal exosomes from patients with septic AKI. Results: Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-offunction assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release, and inflammasome activation. MiR-136-5p was targeted by circ_0001818, and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP, and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p. Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818, miR-136-5p, and TXNIP in serumal exosomes had diagnostic values. Conclusions: Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.

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“…60, NO. 1 (21)(22)(23). Here, we reported that NLRP3 inflammasome was activated in LPS-treated HK2 cells, which was consistent with previous studies (24,25).…”

Section: Discussionsupporting

confidence: 91%

Circ_0001818 Targets Mir-136-5p to Increase Lipopolysaccharide-Induced Hk2 Cell Injuries by Activating Txnip/Nlrp3 Inflammasome Pathway

Feng

Wang

You

et al. 2023

Shock

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“…Apart from cGAS/STING activation, responsible for the inflammatory response, the Ox-mtDNA released via PTP-VDAC channel promotes NLRP3 inflammasome, triggering its assembly in the cytosol. During the NLRP3 inflammasome activation by oligomerization mechanisms, which occur in response to an array of Ox-mtDNA fragments, the Cas-1-mediated cleavage of proinflammatory cytokines, such as interleukin 1β (IL-1β) and interleukin 18 (IL-18), into their mature active forms is triggered [ 55 , 77 ] ( Figure 3 ).…”

Section: Mitochondria Are Potentially a New Target Of Natural Compoun...mentioning

confidence: 99%

Inflammation, Mitochondria and Natural Compounds Together in the Circle of Trust

Nesci

Spagnoletta

Oppedisano

2023

IJMS

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Human diseases are characterized by the perpetuation of an inflammatory condition in which the levels of Reactive Oxygen Species (ROS) are quite high. Excessive ROS production leads to DNA damage, protein carbonylation and lipid peroxidation, conditions that lead to a worsening of inflammatory disorders. In particular, compromised mitochondria sustain a stressful condition in the cell, such that mitochondrial dysfunctions become pathogenic, causing human disorders related to inflammatory reactions. Indeed, the triggered inflammation loses its beneficial properties and turns harmful if dysregulation and dysfunctions are not addressed. Thus, reducing oxidative stress with ROS scavenger compounds has proven to be a successful approach to reducing inflammation. Among these, natural compounds, in particular, polyphenols, alkaloids and coenzyme Q10, thanks to their antioxidant properties, are capable of inhibiting the activation of NF-κB and the expression of target genes, including those involved in inflammation. Even more, clinical trials, and in vivo and in vitro studies have demonstrated the antioxidant and anti-inflammatory effects of phytosomes, which are capable of increasing the bioavailability and effectiveness of natural compounds, and have long been considered an effective non-pharmacological therapy. Therefore, in this review, we wanted to highlight the relationship between inflammation, altered mitochondrial oxidative activity in pathological conditions, and the beneficial effects of phytosomes. To this end, a PubMed literature search was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2014 to 2022.

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“…In the last 20 years, several inflammasomes have been identified [ 38 ]; however, the currently most characterized one is the NLRP3 (NOD-like receptor protein 3) intracellular inflammasome, which belongs to the NOD-like receptor (NLR) family. It is activated in response to several signals and plays an important role in inflammatory diseases, autoimmune diseases, metabolic diseases (metabolic syndrome, obesity, diabetes, and gout), cardiovascular diseases, neurodegenerative diseases (Parkinson’s and Alzheimer’s disease), multiple sclerosis, and also in psychiatric diseases [ 39 , 40 , 41 , 42 ].…”

Section: Autoinflammatory Disease: Since the Beginning Of ’90s A New Branch Of Medicinementioning

confidence: 99%

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

Marcuzzi

Melloni

Zauli

et al. 2021

IJMS

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Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.

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NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

Cited by 24 publications

References 206 publications

Circ_0001818 Targets Mir-136-5p to Increase Lipopolysaccharide-Induced Hk2 Cell Injuries by Activating Txnip/Nlrp3 Inflammasome Pathway

Circ_0001818 Targets Mir-136-5p to Increase Lipopolysaccharide-Induced Hk2 Cell Injuries by Activating Txnip/Nlrp3 Inflammasome Pathway

Inflammation, Mitochondria and Natural Compounds Together in the Circle of Trust

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

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