Increased Superoxide Anion Production in Dermal Fibroblasts of Psoriatic Patients

Er-Raki, Abdelouahed; Charvéron, M.; Bonafé, J. L.

doi:10.1159/000211146

Cited by 14 publications

(4 citation statements)

References 10 publications

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“…Our previous studies showed an increased intracellular ROS production and an enhanced NADPH oxidase activity in fibroblasts obtained from lesional skin of psoriatic patients [6]. This data is in line with the findings of other authors who showed O 2 • − production, mitochondrial superoxide dismutase activity (Mn-SOD) and protein carbonylation level [7,8] to be significantly increased in fibroblasts obtained from involved and uninvolved skin of psoriatic patients in comparison to healthy skin fibroblasts.…”

Section: Introductionsupporting

confidence: 90%

Fibroblasts to Keratinocytes Redox Signaling: The Possible Role of ROS in Psoriatic Plaque Formation

et al. 2019

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Although the role of reactive oxygen species-mediated (ROS-mediated) signalling in physiologic and pathologic skin conditions has been proven, no data exist on the skin cells ROS-mediated communication. Primary fibroblasts were obtained from lesional and non-lesional skin of psoriatic patients. ROS, superoxide anion, calcium and nitric oxide levels and lipoperoxidation markers and total antioxidant content were measured in fibroblasts. NADPH oxidase activity and NOX1, 2 and 4 expressions were assayed and NOX4 silencing was performed. Fibroblasts and healthy keratinocytes co-culture was performed. MAPK pathways activation was studied in fibroblasts and in co-cultured healthy keratinocytes. Increased intracellular calcium, •NO and ROS levels as well as an enhanced NADPH oxidase 4 (NOX4)–mediated extracellular ROS release was shown in lesional psoriatic vs. control fibroblasts. Upon co-culture with lesional fibroblasts, keratinocytes showed p38 and ERK MAPKs pathways activation, ROS, Ca2+ and •NO increase and cell cycle acceleration. Notably, NOX4 knockdown significantly reduced the observed effects of lesional fibroblasts on keratinocyte cell cycle progression. Co-culture with non-lesional psoriatic and control fibroblasts induced slight cell cycle acceleration, but notable intracellular ROS accumulation and ERK MAPK activation in keratinocytes. Collectively, our data demonstrate that NOX4 expressed in dermal fibroblasts is essential for the redox paracrine regulation of epidermal keratinocytes proliferation.

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Section: Introductionsupporting

confidence: 90%

Fibroblasts to Keratinocytes Redox Signaling: The Possible Role of ROS in Psoriatic Plaque Formation

et al. 2019

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“…The key role of dermal fibroblasts in regulating epidermal microenviroment, immune cell behaviour [ 26 , 27 ] and keratinocyte function has been already suggested [ 1 , 5 , 26 , 27 ]. Indeed, impaired fibroblasts can extensively produce superoxide and H 2 O 2 (modifying the redox balance of psoriatic derma), promote inflammatory mechanisms [ 28 ] and may contribute to the epidermal overgrowth by inducing keratinocyte proliferation [ 29 , 30 , 31 , 32 ]. Based on this background, fibroblast cultures derived from psoriatic lesions represent our selected experimental model.…”

Section: Discussionmentioning

confidence: 99%

Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis

Becatti

Barygina

Mannucci

et al. 2018

IJMS

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Psoriasis, a multisystem chronic disease characterized by abnormal keratinocyte proliferation, has an unclear pathogenesis where systemic inflammation and oxidative stress play mutual roles. Dermal fibroblasts, which are known to provide a crucial microenvironment for epidermal keratinocyte function, represented the selected experimental model in our study which aimed to clarify the potential role of SIRT1 in the pathogenetic mechanisms of the disease. We firstly detected the presence of oxidative stress (lipid peroxidation and total antioxidant capacity), significantly reduced SIRT1 expression level and activity, mitochondrial damage and apoptosis (caspase-3, -8 and -9 activities) in psoriatic fibroblasts. Upon SIRT1 activation, redox balance was re-established, mitochondrial function was restored and apoptosis was no longer evident. Furthermore, we examined p38, ERK and JNK activation, which was strongly altered in psoriatic fibroblasts, in response to SIRT1 activation and we measured caspase-3 activity in the presence of specific MAPK inhibitors demonstrating the key role of the SIRT1 pathway against apoptotic cell death via MAPK modulation. Our results clearly demonstrate the involvement of SIRT1 in the protective mechanisms related to fibroblast injury in psoriasis. SIRT1 activation exerts an active role in restoring both mitochondrial function and redox balance via modulation of MAPK signaling. Hence, SIRT1 can be proposed as a specific tool for the treatment of psoriasis.

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“…Although hydrogen peroxide treatment resulted only in a transient and rather weak induction of HO-1 expression in primary keratinocytes [24], and HaCaT cells (the present study), addition of the xenobiotic menadione, which leads to continuous production of superoxide anions, caused a strong and long-lasting expression of HO-1 mRNA and protein. Since large amounts of superoxide anions are continuously generated by inflammatory cells [1] and other cell types [39] in wounded and psoriatic skin, these molecules are likely to be involved in the strong HO-1 expression seen in these tissues. Furthermore, nitric oxide, a potent stimulator of HO-1 expression in keratinocytes and other cell types [40,41], might play a role in HO-1 induction in inflamed skin, since this radical has been shown to be produced in wounded and psoriatic skin [42].…”

Section: Figure 7 Ho-1 Expression Is Upregulated By Hydrogen Peroxidementioning

confidence: 99%

Haem oxygenase-1: a novel player in cutaneous wound repair and psoriasis?

2001

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Haem oxygenase (HO) is the rate-limiting enzyme in the degradation of haem. In addition to its obvious role in iron metabolism, a series of findings indicate an important role for HO in cellular protection against oxidative stress. This effect might be of particular importance during wound healing and also in inflammatory disease. Therefore we determined the expression of the two HO isoenzymes, HO-1 and HO-2, during the healing process of full-thickness excisional wounds in mice. We show a remarkable induction of HO-1 mRNA and protein expression within three days after skin injury. After completion of wound healing, HO-1 expression declined to basal levels. By contrast, expression of HO-2 was not significantly modulated by skin injury. In situ hybridization and immunohistochemistry revealed high HO-1 expression in inflammatory cells of the granulation tissue and in keratinocytes of the hyperproliferative epithelium. A strong overexpression of HO-1 was also observed in the skin of patients suffering from the inflammatory skin disease psoriasis. In addition, HO-2 mRNA levels were increased in the skin of psoriatic patients. Similar to wounded skin, inflammatory cells and keratinocytes of the hyperthickened epidermis were the major producers of HO-1 in psoriatic skin. In vitro studies with cultured keratinocytes revealed a potential role for reactive oxygen species (ROS), but not for growth factors and pro-inflammatory cytokines, as inducers of HO-1 expression in inflamed skin. Our findings suggest a novel role for HO in wound healing and inflammatory skin disease, where it might be involved in haem degradation and in the protection of cells from the toxic effects of ROS.

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Increased Superoxide Anion Production in Dermal Fibroblasts of Psoriatic Patients

Cited by 14 publications

References 10 publications

Fibroblasts to Keratinocytes Redox Signaling: The Possible Role of ROS in Psoriatic Plaque Formation

Fibroblasts to Keratinocytes Redox Signaling: The Possible Role of ROS in Psoriatic Plaque Formation

Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis

Haem oxygenase-1: a novel player in cutaneous wound repair and psoriasis?

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