BAY 11-7082 inhibits the NF-κB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis

Irrera, Natasha; Vaccaro, Mario; Bitto, Alessandra; Pallio, Giovanni; Pizzino, Gabriele; Lentini, Maria; Arcoraci, Vincenzo; Minutoli, Letteria; Scuruchi, Michele; Cutroneo, Giuseppina; Anastasi, Giuseppe; Ettari, Roberta; Squadrito, Francesco; Altavilla, Domenica

doi:10.1042/cs20160645

Cited by 105 publications

(67 citation statements)

References 36 publications

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“…NF-κB in macrophages can upregulate NLRP3 expression (20). Intracellular inflammatory factors, such as IL-1β, can also be released out of the cell, thus inducing inflammatory response (22). In the present study, addition of an NLRP3 inhibitor reversed the miR-155 mediated increased inflammation in keratinocyte-induced HaCaT cells.…”

Section: Discussionsupporting

confidence: 51%

Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation

Luo

Zeng

et al. 2018

Int J Mol Med

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Psoriasis is a dermatosis with the major clinical symptoms of scale, erythema and itching, and it has a long disease course. In addition, it is easily recurrent and refractory, greatly affecting the physical and mental health of patients. In the present study, it was hypothesized that the function of miR‑155 increases psoriasis‑induced inflammation and that its expression may be dependent on inflammasome activation. miR‑155 expression was examined by gene chip array and quantitative polymerase chain reaction analysis. miR‑155 expression levels were significantly increased in an in vivo model of psoriasis compared with normal tissues, as was the expression of NLR family pyrin domain containing 3 (NLRP3). In vitro, using keratinocyte‑induced HaCaT cells as a model for psoriasis, silencing of miR‑155 was confirmed to significantly decrease inflammation and NLRP3/caspase‑1 signaling. Activation of toll‑like receptor 4 (TLR4) enhanced the miR‑155‑induced inflammatory response in the in vitro keratinocyte model. Treatment with a TLR4 inhibitor or an NLRP3 inhibitor reversed the miR‑155‑mediated inflammation in the same cell system. The present study demonstrated that miR‑155 silencing suppressed psoriasis‑associated inflammatory responses through inflammasome NLRP3 regulation.

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Section: Discussionsupporting

confidence: 51%

Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation

Luo

Zeng

et al. 2018

Int J Mol Med

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“…A previous experiment has already demonstrated that the expression of the phosphorylated transcriptional factor NF-κB and consequently of the pro-inflammatory cytokine TNF-α increases following IMQ administration because of an inflammatory process triggering [13]. In this experimental setting too, mice challenged with IMQ showed an enhanced expression of both pNF-κB and TNF-α.…”

Section: Pdrn Reduces Both Pnf-κb and Pro-inflammatory Cytokines Exprmentioning

confidence: 75%

PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation

Irrera

Bitto

Vaccaro

et al. 2020

IJMS

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Nuclear factor-κB (NF-κB) plays a central role in psoriasis and canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-κB and boosts the Wnt/β-catenin signaling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Psoriasis-like lesions were induced by a daily application of imiquimod (IMQ) on the shaved back skin of mice for 7 days. Animals were randomly assigned to the following groups: Sham psoriasis challenged with Vaseline; IMQ animals challenged with imiquimod; and IMQ animals treated with PDRN (8 mg/kg/ip). An additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. PDRN restored a normal skin architecture, whereas istradefylline abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pro-inflammatory cytokines, prompted Wnt signaling, reduced IL-2 and increased IL-10. PDRN also reverted the LPS repressed Wnt-1/β-catenin in human keratinocytes and these effects were abolished by ZM241385, an A2A receptor antagonist. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. PDRN anti-psoriasis potential may be linked to a “dual mode” of action: NF-κB inhibition and Wnt/β-catenin stimulation.

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“…It suggests that IL-17A-mediated inflammatory actions in Koebner phenomenon are dependent on the activation of p38 MAPK and NF-κB [21]. Indeed, NF-kB has been reported as a key transcriptional factor of psoriasis [81,82] and different pharmacological agents including quercetin and BAY 11-7082 are shown to inhibit the development of psoriatic lesion by inhibiting the activation of this transcriptional factor [83].…”

Section: Il-17 Nf-kb and Signal Transducer And Activator Of Transcrmentioning

confidence: 99%

Koebner phenomenon leading to the formation of new psoriatic lesions: evidences and mechanisms

Liu

2019

Bioscience Reports

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Koebner phenomenon refers to the emergence of new psoriatic lesions in the healthy skin regions following an injury/trauma to psoriatic patients. The occurrence of psoriatic lesions at unusual areas of the body regions such as on penis, around eyes and on keloids suggest that the Koebner phenomenon may be responsible for these lesions. A number of agents/triggers have been reported to induce the development of new psoriatic lesions in healthy skin areas and these include, tattooing skin, radiations, skin incision, viral infections and striae etc. The different mechanisms that contribute in inducing the development of new psoriatic lesions as Koebernization include the involvement of mast cell-derived inflammatory mediators such as tryptase, IL-6, IL-8, IL-17, and IL-36γ. Moreover, an increased expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) also contribute in Koebernization. Apart from these, there is a critical role of α 2 β1 integrins, S100A7 (psoriasin) and S100A15 (koebnerisin), change in the ratio of CD4+/CD8+ T cells, down-regulation of mechanosensitive polycystin 1 protein, decrease in inflammation controlling atypical chemokine receptor 2 (ACKR2), reduced expression of N-methyl-d-aspartate (NMDA) receptors (NMDARs) on the keratinocytes and increase in levels of chemokines (CXCL8 and CCL20) in inducing formation of new psoriatic lesions. The present review discusses the role of Koebner phenomenon in the development of new psoriatic lesions. Moreover, it also describes the mechanisms involved in Koebernization in the form of discussion of different key targets that may be potentially modulated pharmacologically to attenuate/halt the development of new psoriatic lesions.

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BAY 11-7082 inhibits the NF-κB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis

Cited by 105 publications

References 36 publications

Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation

Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation

PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation

Koebner phenomenon leading to the formation of new psoriatic lesions: evidences and mechanisms

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