Pro-oxidant status and Nrf2 levels in psoriasis vulgaris skin tissues and dimethyl fumarate-treated HaCaT cells

Lee, Yoon Jin; Bae, Jin Ho; Kang, Sang Gue; Cho, Sung Woo; Chun, Dong-Il; Nam, Seung Min; Kim, Chul Han; Nam, Heerim; Lee, Seon Hwa; Lee, Sang‐Han; Cho, Moon Kyun

doi:10.1007/s12272-017-0955-5

Cited by 31 publications

(26 citation statements)

References 47 publications

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“…DMF, dimethyl fumarate; I/R, ischemia-reperfusion; MPO, myeloperoxidase types of cells, including keratinocytes, fibroblasts, endothelial cells, neuron cells. 25,31,34,35 We newly found the antioxidative effect of DMF on H 2 O 2 -derived ROS in mouse pericytes-like cells in vitro.…”

Section: Dmf Suppressed Ros Production Caused By Oxidative Stress Imentioning

confidence: 89%

Protective effect of dimethyl fumarate for the development of pressure ulcers after cutaneous ischemia‐reperfusion injury

Inoue

Uchiyama

Sekiguchi

et al. 2020

Wound Repair Regeneration

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Ischemia‐reperfusion (I/R) is associated with various pathogenic conditions, and there has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non‐blanchable erythema. Several studies demonstrated that oxidative stress is a key player in I/R injury, and the inhibition of oxidative stress may be capable of protecting tissue damage after I/R injury in various organs including skin. Dimethyl fumarate (DMF) approved by the Food and Drug Administration is Nrf2 activator, and recent studies revealed the antioxidative and anti‐inflammatory effects of DMF on I/R injury in animal models. Our objective was to assess the effects of oral administration of DMF on the development of PUs after cutaneous I/R injury in mice. We found that DMF administration significantly decreased the size of PUs after cutaneous I/R. Cutaneous I/R‐induced oxidative stress was also significantly inhibited by DMF in OKD48 mice, in which oxidative stress can be visually assessed. In addition, DMF treatment decreased hypoxic area, the numbers of apoptotic cells, and vascular loss in I/R area. DMF treatment suppressed the infiltration of MPO+ neutrophils and the production of proinflammatory cytokines in I/R site after cutaneous I/R injury. in vitro experiments, DMF treatment suppressed the production of reactive oxygen species in pericyte‐like cells. These results suggest that DMF treatment might prevent the formation of PUs induced by cutaneous I/R injury via suppressing oxidative stress and subsequent inflammation. DMF treatment during the early phase of decubitus ulcers might protect against further progression.

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Section: Dmf Suppressed Ros Production Caused By Oxidative Stress Imentioning

confidence: 89%

Protective effect of dimethyl fumarate for the development of pressure ulcers after cutaneous ischemia‐reperfusion injury

Inoue

Uchiyama

Sekiguchi

et al. 2020

Wound Repair Regeneration

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“…Additional confirmation of the role of oxidative stress in the course of Ps are the results of clinical trials in which antioxidant supplementation resulted in a significant improvement in general status of psoriatic patients [59]. So far, systemic changes at the transcription level have not been studied, and only the local reduction of Nrf2 transcriptional activity in the skin of psoriasis patients has been found [24]. Therefore, Nrf2 transcriptional activity reduced in inflammatory cells of our patients with PsA suggest this could be important pathophysiological parameter specific for this type of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it is suggested that oxidative stress may activate mechanisms that restore the redox balance, including activation of Nrf2 transcription factor, which is responsible for antioxidant and cytoprotective gene transcription [22,23]. However, a reduction in Nrf2 activity was observed in the skin of psoriatic patients [24].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

Ambrożewic¹,

Wójcik²,

Wroński³

et al. 2018

Preprint

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Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects.The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis.This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

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“…Persistent overactivation of AHR by TCDD and other dioxin-related compounds induces prolonged oxidative stress and may cause chloracne (51,68,69). The generation of ROS is also involved in the pathogenesis of contact dermatitis, AD and psoriasis (70)(71)(72). Therefore, antioxidative AHR agonists may be beneficial for the treatment of oxidative inflammatory skin diseases.…”

Section: Regulatory Role Of Aryl Hydrocarbon Receptor In Oxidative Stmentioning

confidence: 99%

Antioxidative Phytochemicals Accelerate Epidermal Terminal Differentiation via the AHR-OVOL1 Pathway: Implications for Atopic Dermatitis

Furue¹,

Hashimoto-Hachiya²,

Tsuji³

2018

Acta Derm Venerol

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Aryl hydrocarbon receptor (AHR) is a chemical sensor that is expressed abundantly in epidermal keratinocytes. Oxidative AHR ligands induce the production of reactive oxygen species. However, antioxidant AHR ligands inhibit reactive oxygen species generation via activation of nuclear factor-erythroid 2-related factor-2, which is a master switch for antioxidative signalling. In addition, AHR signalling accelerates epidermal terminal differentiation, but excessive acceleration by oxidative ligands, such as dioxins, may induce chloracne and inflammation. However, antioxidative phytochemical ligands induce the beneficial acceleration of epidermal differentiation that repairs skin barrier disruption. The upregulated expression of differentiation molecules, such as filaggrin, is mediated via the AHR-OVOL1 axis. This AHR-OVOL1 system is capable of counteracting skin barrier dysfunction in T-helper type 2-shifted inflammation. This article reviews the dynamic and multifaceted role of AHR in epidermal biology and discusses the potential use of antioxidative phytochemical ligands for AHR in inflammatory skin diseases, such as atopic dermatitis.

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Pro-oxidant status and Nrf2 levels in psoriasis vulgaris skin tissues and dimethyl fumarate-treated HaCaT cells

Cited by 31 publications

References 47 publications

Protective effect of dimethyl fumarate for the development of pressure ulcers after cutaneous ischemia‐reperfusion injury

Protective effect of dimethyl fumarate for the development of pressure ulcers after cutaneous ischemia‐reperfusion injury

Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

Antioxidative Phytochemicals Accelerate Epidermal Terminal Differentiation via the AHR-OVOL1 Pathway: Implications for Atopic Dermatitis

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