EFLA 945 restricts AIM2 inflammasome activation by preventing DNA entry for psoriasis treatment

Chung, I‐Che; Yuan, Sheng-Ning; OuYang, Chun‐Nan; Hu, Sheng-I; Lin, Hsin‐Chung; Huang, Kuo‐Yang; Lin, Wei‐Ning; Chuang, Yu-Ting; Chen, Yu-Jen; Ojcius, David M.; Chang, Yu‐Sun; Chen, Lih‐Chyang

doi:10.1016/j.cyto.2019.154951

Cited by 25 publications

(15 citation statements)

References 37 publications

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“…Dermal cathelicidin LL-37 binds self-DNA and triggers cutaneous inflammation by activation of dermal plasmacytoid dendritic cells, while epidermal LL-37 joins with cytosolic DNA in keratinocytes and blocks its pro-inflammatory activity [ 24 , 25 ]. This may explain why vitamin D3, a strong inducer of cathelicidin expression in keratinocytes and monocytes, is effective for psoriasis and reduces inflammation in psoriatic lesions [ 23 ].…”

Section: The Aim2 Inflammasome (In Psoriasis)mentioning

confidence: 99%

“…Reaffirming the role of inflammasomes as a potential therapeutic target in the treatment of psoriasis [ 9 ], as with the NLRP3 inflammasome, researchers focused on finding substances that would silence or completely inhibit AIM-2 inflammasome activation in psoriasis. In 2020, Ching et al demonstrated in IMQ-induced psoriasis models that red vine leaf extract (EFLA 945) may interfere with the activation of AIM2 and other inflammasomes; therefore, it has obvious potential in the treatment of psoriasis [ 24 ].…”

Section: The Aim2 Inflammasome (In Psoriasis)mentioning

confidence: 99%

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The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

Ciążyńska

Olejniczak-Staruch

Sobolewska-Sztychny

et al. 2021

IJMS

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Inflammasomes are high-molecular-weight protein complexes that may cleave the two main proinflammatory cytokines, pro-interleukin-1β and pro-interleukin-18, into active forms, and contribute to psoriasis. Despite recent advances made in the pathogenesis of psoriasis, mainly studied as an autoimmune condition, activation of immune response triggers of psoriasis is still not completely understood. Recently, focus was placed on the role of inflammasomes in the pathogenesis of psoriasis. Multiple types of inhibitors and activators of various inflammasomes, inflammasome-related genes, and genetic susceptibility loci were recognized in psoriasis. In this systemic review, we collect recent and comprehensive evidence from the inflammasomes, NLRP1, NLRP3, and AIM2, in pathogenesis of psoriasis.

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Section: The Aim2 Inflammasome (In Psoriasis)mentioning

confidence: 99%

Section: The Aim2 Inflammasome (In Psoriasis)mentioning

confidence: 99%

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

Ciążyńska

Olejniczak-Staruch

Sobolewska-Sztychny

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Consequently, the EFLA ® 945 containing resveratrol can limit the activation of AIM2 inflammasome. In a rat model, the EFLA ® 945 had reduced inflammatory responses caused by psoriasis, including CASP-1 activation, IL-1β secretion, and IL-17 production (27). The IL-1β production following the NLRP3 activation due to the monocyte/macrophage treatment with monosodium urate (MSU) was also shown to be responsible for the pathogenesis of gouty arthritis.…”

Section: Other Studies On the Effect Of Resveratrol On Inflammasomementioning

confidence: 99%

Resveratrol; an inflammasome inhibitor and a potential therapy for severe cases of COVID-19

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 126 million people worldwide and deaths exceed two million. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing coronavirus disease 2019 (COVID-19) immunopathogenesis have remained uncertain. Severe COVID-19 is associated with a cytokine storm, chronic inflammation, neutrophilia, lymphocyte dysfunction, lymphopenia, reduction in T-lymphocytes and natural killer (NK) cells, disruption in viral clearance, and neutrophil/macrophage infiltration in the lungs. In many cases, patients develop acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and/or multiple-organ dysfunction syndrome (MODS). Resveratrol reduces the expression of inflammasome activators such as thioredoxin-interacting protein (TXNIP) and nuclear factor erythroid 2 (NrF2) and increases that of the inflammasome inhibitor, i.e., NAD-dependent deacetylase sirtuin-1 (SIRT1). Resveratrol is able to inhibit the production of reactive oxygen species (ROS) and the activation of inducible nitric oxide synthases (iNOS). It affects signaling pathways including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-ĸB) thereby further inhibiting inflammasomes. Because of its anti-inflammasome, anti-inflammatory, and anti-oxidant effects and considering the key role of inflammation and cytokine storm in disease severity and poor patient outcomes, it is concluded that resveratrol can be useful in the treatment of COVID-19. Given the persistence of the COVID-19 pandemic and the challenges of extensive vaccination in all countries, it is important to achieve more effective treatments to decrease the mortality rate and severity of severe injuries following COVID-19. Given all the effects reviewed in this article, resveratrol at a dose of up to 600 mg per day can be exploited as a potential adjunctive therapy for COVID-19 patients.

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“…Because murine keratinocytes do not express pro-IL-1β, IL-18 is the only cytokine that can be cleaved into its active form by inflammasomes in these cells (114). Recently, Chung reported that red vine leaf extract (EFLA 945) greatly attenuated IMQ-induced psoriasis phenotypes by inhibiting the activity of the AIM2 inflammasome (105). Epigallocatechin-3-gallate (EGCG) has been shown to inhibit AIM2-induced inflammatory cytokines, and attenuate caspase-1 activation in interferon gamma-primed HEKn cells (104).…”

Section: The Aim2 Inflammasome In Psoriasismentioning

confidence: 99%

Inflammasomes in Common Immune-Related Skin Diseases

Tang

Zhou

2020

Front. Immunol.

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The inflammasome is an important protein complex that cleaves the proinflammatory cytokines pro-IL-1β and pro-IL-18 into their active forms. Owing to its critical role in eliciting innate immune responses, IL-1β has been suggested to contribute to various skin diseases, including psoriasis, vitiligo, systemic lupus erythematosus (SLE), and atopic dermatitis (AD). Recently, several types of activators and inhibitors of different inflammasomes, as well as inflammasome-related genes and genetic susceptibility loci, have been identified in these immune-related common skin diseases. In particular, inflammasome activators and inhibitors presented highly cell-type-specific activity, suggesting that the inflammasome might perform different functions in different cell types. Moreover, most of these findings were based on experimental disease models, and the clinical features of the models partly resemble the typical symptoms of the diseases. In this review, from the perspective of activators and inhibitors, we collected evidence from the widely-studied inflammasomes, NLRP3, AIM2, and NLRP1, in psoriasis, vitiligo, SLE, and AD. Importantly, some small-molecule inhibitors hold therapeutic promise for the treatment of these diseases.

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EFLA 945 restricts AIM2 inflammasome activation by preventing DNA entry for psoriasis treatment

Cited by 25 publications

References 37 publications

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

Resveratrol; an inflammasome inhibitor and a potential therapy for severe cases of COVID-19

Inflammasomes in Common Immune-Related Skin Diseases

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