Under‐expression of VHL and over‐expression of HDAC‐1, HIF‐1α, LL‐37, and IAP‐2 in affected skin biopsies of patients with psoriasis

Tovar-Castillo, Laura; Cancino‐Díaz, Juan C.; García-Vázquez, Francisco; Cancino-Gómez, Francisco G.; León-Dorantes, Gladys; Blancas-González, Fernando; Jiménez-Zamudio, L; Garcı́a-Latorre, Ethel; Cancino-Díaz, Mario E.

doi:10.1111/j.1365-4632.2006.02962.x

Cited by 85 publications

(68 citation statements)

References 24 publications

(53 reference statements)

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“…8). The current data partly corroborate the findings of previous studies, which showed that psoriatic skin contained high amounts of the antimicrobial peptide cathelicidin/LL-37 (48). LL-37 potently activates plasmacytoid dendritic cells to produce type 1 IFNs by binding nonstimulatory self-DNA and causing it to adopt an aggregated and condensed structure (49).…”

Section: Discussionsupporting

confidence: 81%

Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via Scaffolding Protein p62/SQSTM1

Lee

Shin

Yuk

et al. 2011

The Journal of Immunology

182

169

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The scaffolding adaptor protein p62/SQSTM1 (p62) has been shown to be an autophagy receptor that acts as a link between the ubiquitination and autophagy machineries. However, the roles of autophagy and p62 in human keratinocytes are not well understood. In this study, we show that keratinocyte autophagy negatively regulates p62 expression, which is essential for the prevention of excessive inflammation and the induction of cathelicidin in human keratinocytes. Stimulation of TLR2/6 or TLR4 in primary human keratinocytes robustly activated autophagy pathways and up-regulated p62 expression through induction of NADPH oxidases 2 and 4 and the generation of reactive oxygen species. MyD88 and TNFR-associated factor 6, key signaling molecules that mediate TLR activation, played an essential role in the induction of autophagy and p62 expression. Additionally, blockade of autophagy significantly increased the generation of inflammatory cytokines and expression of p62 in primary human keratinocytes. Notably, silencing hp62 through RNA interference resulted in a significant decrease in NF-κB activation, inflammatory cytokine production, cathelicidin expression, and cell proliferation (as well as cyclin D1 expression) in keratinocytes. Epidermal expression of p62 was further found to be significantly higher in psoriatic skin than in skin affected by atopic dermatitis or from healthy controls. Collectively, our data provide new insights into the roles of autophagy and p62 in controlling cutaneous inflammation.

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Section: Discussionsupporting

confidence: 81%

Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via Scaffolding Protein p62/SQSTM1

Lee

Shin

Yuk

et al. 2011

The Journal of Immunology

182

169

View full text Add to dashboard Cite

show abstract

“…It would be interesting to examine expression of HDAC3 in human dermal microvascular endothelial cells and the role of HDAC3 in inflammatory response. Human psoriatic skin shows overexpression of HDAC1 (32). These reports suggest a potential role of HDAC(s) in human skin inflammatory diseases.…”

Section: Discussionmentioning

confidence: 87%

Histone Deacetylase 3 Mediates Allergic Skin Inflammation by Regulating Expression of MCP1 Protein

Kim¹,

Kim²,

Park³

et al. 2012

Journal of Biological Chemistry

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“…10 Interestingly, analysis of skin biopsies from patients with psoriasis shows that c-Jun and pVHL are downregulated in psoriatic skin. 33,34 Furthermore, a mouse model of psoriasis is also deficient in epidermal Jun proteins. 35 In view of these supporting evidence, it will be worth to examine the expression or activity of TAK1 in human psoriatic skin biopsies.…”

Section: Discussionmentioning

confidence: 99%

TAK1 regulates SCF expression to modulate PKBα activity that protects keratinocytes from ROS-induced apoptosis

Lam

Tan

et al. 2011

Cell Death Differ

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Dysregulated reactive oxygen species (ROS) generation contributes to many human pathologies, including cancer and diabetes. During normal wound repair, inflammation-induced ROS production must be tightly controlled, but the mechanisms reining their generation remain unclear. Herein, we show that transforming growth factor b-activated kinase 1 (TAK1) directly regulates stem cell factor (SCF) expression, which activates the protein kinase B (PKB)a pro-survival pathway in a cell-autonomous manner to protect keratinocytes from ROS-mediated cell death. TAK1 is a pivotal inflammatory mediator whose expression was transiently elevated during wound healing, paralleling the ROS production profile. TAK1 deficiency in keratinocytes led to increased apoptosis in response to anoikis and TNF-a treatment and was associated with elevated ROS level as analyzed by FACS. Using organotypic skin co-culture and comparative growth factor array analysis, we revealed a cell-autonomous mechanism that involved the SCF/c-Kit/PKBa signaling cascade. Ectopic expression of TAK1 or treatment with exogenous recombinant SCF restored the increased ROS production and apoptotic cell death in TAK1-deficient keratinocytes. Conversely, normal keratinocytes treated with various inhibitors targeting the SCF/c-Kit/PKBa pathway exhibited increased ROS production and TNF-a-or anoikis-induced apoptosis. Our study reveals a novel anti-apoptotic role for SCF in keratinocytes and identifies TAK1 as a novel player uniting inflammation and ROS regulation in skin redox biology.

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Under‐expression of VHL and over‐expression of HDAC‐1, HIF‐1α, LL‐37, and IAP‐2 in affected skin biopsies of patients with psoriasis

Abstract: These findings suggest that there could be an association of HDAC-1, HIF-1alpha, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.

Cited by 85 publications

References 24 publications

Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via Scaffolding Protein p62/SQSTM1

Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via Scaffolding Protein p62/SQSTM1

Histone Deacetylase 3 Mediates Allergic Skin Inflammation by Regulating Expression of MCP1 Protein

TAK1 regulates SCF expression to modulate PKBα activity that protects keratinocytes from ROS-induced apoptosis

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