Journal Of Investigative Dermatology

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TWEAK/Fn14 Interaction Confers Aggressive Properties to Cutaneous Squamous Cell Carcinoma

Thu, 2018-11-08 00:00
Recent studies showed that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) signaling participates in the progression of internal malignancies. However, its role in the biological properties of cutaneous squamous cell carcinoma (SCC) remains unclear. This study was designed to explore the effect of TWEAK/Fn14 activation on cutaneous SCC as well as the relevant mechanism. The expression of TWEAK and Fn14 was determined in tissue samples of patients with cutaneous SCC.

A preclinical model for studying herpes simplex virus infection

Thu, 2018-11-08 00:00
Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these drugs are a clinical problem among immunocompromised patients. To provide more efficient therapy and to counteract resistance, a different class of antiviral compounds has been developed. Pritelivir, a helicase primase inhibitor, represents a promising candidate for improved therapy. Here, we established a HSV-1 infection model on microneedle-pretreated human skin ex vivo.

The regulation of skin fibrosis in systemic sclerosis by extracellular ATP via P2Y2 purinergic receptor

Sun, 2018-11-04 00:00
Tissue injury/hypoxia and oxidative stress induced-extracellular ATP can act as a damage-associated molecular pattern molecules (DAMPs), which initiates inflammatory response. Objective was to elucidate the role of extracellular ATP in skin fibrosis in systemic sclerosis (SSc). We identified that hypoxia enhanced ATP release, and extracellular ATP enhanced IL-6 production more significantly in SSc fibroblasts than in normal fibroblasts. There were no significant differences of P2X and P2Y receptors expressions between normal and SSc fibroblasts.

Aging in skin of color: Disruption to elastic fiber organization is detrimental to skin’s biomechanical function

Sun, 2018-11-04 00:00
Skin aging is a complex process involving the additive effects of time-dependent intrinsic aging and changes elicited via skin’s interaction with the environment. Maintaining optimal skin function is essential for healthy aging across global populations; yet most research focuses on lightly-pigmented skin (Fitzpatrick phototypes I-III), with little emphasis on skin of color (Fitzpatrick phototypes V–VI). Here, we explore the biomechanical and histologic consequences of aging in black African-American volunteers.

The calcium-sensing receptor regulates epidermal intracellular Ca2+ signaling and re-epithelialization after wounding

Sun, 2018-11-04 00:00
Extracellular Ca2+ (Ca2+o) is a crucial regulator of epidermal homeostasis and its receptor, the Ca2+-sensing receptor (CaSR), conveys the Ca2+o signals to promote keratinocyte adhesion, differentiation, and survival via activation of intracellular Ca2+ (Ca2+i) and E-cadherin-mediated signaling. Here, we took genetic loss-of-function approaches to delineate the functions of CaSR in wound re-epithelialization. Cutaneous injury triggered a robust CaSR expression and a surge of Ca2+i in epidermis. CaSR and E-cadherin were co-expressed at the cell-cell membrane between migratory keratinocytes in the nascent epithelial tongues.

Pharmacological inhibition of serine palmitoyl transferase and sphingosine kinase-1/-2 inhibits Merkel Cell Carcinoma cell proliferation

Sat, 2018-11-03 00:00
The majority of Merkel cell carcinoma (MCC), a highly aggressive neuroendocrine cancer of the skin, is associated with Merkel cell polyomavirus (MCPyV) infection. Polyomavirus binding, internalization and infection is mediated by glycosphingolipids (GSL). Besides receptor function, bioactive sphingolipids (SL) are increasingly recognized as potent regulators of several hallmarks of cancer. MCPyV+ and MCPyV- cells express serine palmitoyltransferase (SPT) subunits and sphingosine kinase (SK)1/2 mRNA.

Potentiation of psoriasis-like inflammation by PCSK9

Fri, 2018-11-02 00:00
Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of low-density lipoprotein(LDL). Proprotein convertase subtilisin/kexin 9 (PCSK9), promoting the degradation of LDL receptors, and therefore the increased concentration of circulating LDL, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying siRNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients, the imiquimod (IMQ) induced psoriatic reactions in Pcsk9 knockout and Pcsk9 siRNA treated mice, and also used cultured human keratinocytes to investigate the role of PCSK9 on regulating cell proliferation and apoptosis.

Culprit drugs induce specific IL-36 overexpression in Acute Generalized Exanthematous Pustulosis

Fri, 2018-11-02 00:00
Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous drug reaction. Although an involvement of drug-specific T cells has been reported, the physiopathology of AGEP and mechanism of neutrophilic skin inflammation remains incompletely understood. Recently, mutations in IL-36RN, the gene encoding the IL-36 receptor antagonist, have been reported to be more frequent in AGEP patients and pustular psoriasis. Here, we show that IL-36 cytokines, in particular IL-36γ, is highly expressed in lesional skin of AGEP patients, keratinocytes and macrophages being a major source of IL-36γ.

Granzyme K Expressed by Classically Activated Macrophages Contributes to Inflammation and Impaired Remodeling

Fri, 2018-11-02 00:00
Granzyme K (GzmK), traditionally described as a pro-apoptotic, granule-secreted serine protease, has been proposed to promote inflammation. Found at low levels in the plasma of healthy individuals, GzmK is markedly elevated in response to sepsis and infection. In the present study we investigated the role of GzmK in inflammation and remodeling in response to thermal injury. In human burn tissue, GzmK was elevated compared to normal skin, with expression predominantly found in macrophages. GzmK was expressed and secreted by cultured human classically-activated macrophages.

Phosphatidylglycerol inhibits toll-like receptor-mediated inflammation by danger-associated molecular patterns

Thu, 2018-11-01 00:26
Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously demonstrated that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to anti-microbial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (DAMPs) to activate TLRs and the innate immune system.

Table of Contents

Thu, 2018-11-01 00:00

Subscription Information

Thu, 2018-11-01 00:00

Editorial Board

Thu, 2018-11-01 00:00

Editors’ Picks

Thu, 2018-11-01 00:00
Cutaneous squamous cell carcinoma (SCC) has the clinical and molecular features of a tumor that is likely to respond to systemic immunotherapy, as this tumor harbors a high mutational load and incidence is increased in immunocompromised patients. While nearly all cases are cured with surgery, in the remaining 5%, the tumor becomes metastatic or locally advanced, requiring palliative systemic therapy due to a lack of efficacious approved systemic therapies. In early phase I trials, the human monoclonal antibody to programmed death-1 (PD-1), cemiplimab, elicited a durable response in patients with advanced disease.

Clinical Snippets

Thu, 2018-11-01 00:00
The opportunistic skin bacterium Propionibacterium acnes has been linked to acne vulgaris, a condition that affects more than 40 million people in the United States and has mostly inadequate or intolerable therapies. Following prior studies indicating that the P. acnes secretory virulence factor Christie-Atkins-Munch-Peterson (CAMP) factor is the main source of inflammation in acne vulgaris, Wang and colleagues demonstrated that a vaccination strategy targeting CAMP factor reduced the growth of P. acnes, diminished associated erythema, and limited production of proinflammatory cytokines in mice.

Research Techniques Made Simple: Transepidermal Water Loss Measurement as a Research Tool

Thu, 2018-11-01 00:00
Transepidermal water loss (TEWL) is the most widely used objective measurement for assessing the barrier function of skin in healthy individuals but also patients with skin diseases that are associated with skin barrier dysfunction, such as atopic dermatitis. TEWL is the quantity of condensed water that diffuses across a fixed area of stratum corneum to the skin surface per unit time. The water evaporating from the skin is measured using a probe that is placed in contact with the skin surface and contains sensors that detect changes in water vapor density.

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