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Journal of Investigative Dermatology

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https://www.readbyqxmd.com/read/30031029/hsp70i-q435a-encoding-dna-repigments-vitiligo-lesions-in-sinclair-swine
#1
Steven W Henning, Manuel F Fernandez, James Mahon, Richard Duff, Farshid Azarafrooz, José A Guevara-Patiño, Alfred W Rademaker, Andrew Salzman, I Caroline Le Poole
Human HSP70iQ435A carries a single amino acid modification within the dendritic cell (DC) activating region and tolerizes DCs in vitro. The underlying DNA was used to prevent and treat disease in vitiligo mouse models through reduced dendritic cell activation and diminished skin T cell infiltration, suggesting the same may be useful for patients. Physiologic differences between mouse and human skin then called for studies in large animals with human-like skin. We established the efficiency of DNA jet injection into swine skin before subcloning HSP70iQ435A into clinically suitable vector pUMVC3...
July 18, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30030153/hmgb1-rage-mediates-uvb-induced-secretory-inflammatory-response-and-resistance-to-apoptosis-in-human-melanocytes
#2
K Zhang, G Anumanthan, S Scheaffer, L A Cornelius
The major modifiable risk factor in melanomagenesis is UV exposure and mutagenesis of melanocytes. Other UV-induced events that contribute to early tumorigenesis are poorly understood. Herein we show the repeated exposure of human primary melanocytes to UVB results in a sustained senescence response, increases in expression of STAT1, MX1, OAS2 and IRF7 proteins of up to 75-fold, and resistance to subsequent UVB-induced apoptosis. In the setting of UVB-induced DNA damage, we detected time-dependent increases in the release of damage-associated molecular patterns (DAMPs) such as HMGB1...
July 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30030152/chronic-inflammation-promotes-skin-carcinogenesis-in-cancer-prone-discoid-lupus-erythematosus
#3
Anniek Zaalberg, Sara Moradi Tuchayi, Amir H Ameri, Kenneth H Ngo, Trevor J Cunningham, Jean-Pierre Eliane, Maia Livneh, Thomas D Horn, Ilana S Rosman, Amy Musiek, Milan J Anadkat, Shadmehr Demehri
High-risk skin cancer is a rare, but severe, complication associated with discoid lupus erythematosus (DLE). Chronic scar, inflammation, ultraviolet radiation and immunosuppressive medications are proposed explanations for this heightened skin cancer risk; however, the exact mechanism driving skin carcinogenesis in DLE is unknown. The distinct co-localization of multiple independent skin cancers with areas of active inflammation in two DLE patients followed over eight years strongly suggested that lupus inflammation promotes skin carcinogenesis in DLE...
July 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30030151/a-framework-for-multi-omic-prediction-of-treatment-response-to-biologic-therapy-for-psoriasis
#4
Amy C Foulkes, David S Watson, Daniel F Carr, John G Kenny, T Slidel, Richard Parslew, Munir Pirmohamed, Simon Anders, Nicholas J Reynolds, Christopher E M Griffiths, Richard B Warren, Michael R Barnes
Biologic therapies have shown high efficacy in psoriasis, but individual response varies and is poorly understood. To inform biomarker discovery in the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) study, we evaluated a comprehensive array of omics platforms across three time-points and multiple tissues in a pilot investigation of ten severe psoriasis patient, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used RNA-sequencing to analyse mRNA and small-RNA transcriptome in blood, lesional and non-lesional skin and the Somascan platform to investigate the serum proteome...
July 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30030150/generation-and-validation-of-a-complete-knockout-model-of-abcc6a-in-zebrafish
#5
M Van Gils, A Willaert, E Y G De Vilder, P Coucke, O M Vanakker
Pseudoxanthoma elasticum is an ectopic mineralization disease due to biallelic ABCC6 mutations. As no treatment options are currently available a reliable zebrafish model is invaluable for high throughput compound screening. However, data from previously reported knockdown and mutant zebrafish models for abcc6a, the functional orthologue of ABCC6, showed phenotypic discrepancies. To address this, we developed a complete abcc6a knockout model using CRISPR/Cas9 and compared its phenotype to that of a mutant model (Sa963) and a splice junction morpholino model...
July 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30009831/cxcl5-as-regulator-of-neutrophil-function-in-cutaneous-melanoma
#6
Agnes Forsthuber, Katharina Lipp, Liisa Andersen, Stefanie Ebersberger, Osvaldo Graña-Castro, Wilfried Ellmeier, Peter Petzelbauer, Beate M Lichtenberger, Robert Loewe
Chemokines mold the tumor microenvironment by recruiting distinct immune cell populations, thereby strongly influencing disease progression. Previously, we showed that CXCL5 expression is upregulated in advanced stages of primary melanomas, which correlates with the presence of neutrophils in the tumor. Analysis of neutrophil populations in various tissues revealed a distinct phenotype of tumor associated neutrophils (TANs). TANs expressed PD-L1, CXCR4, CCR5, Adam17, Nos2 and were immunosuppressive in a T cell proliferation assay...
July 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30009830/insights-into-male-androgenetic-alopecia-differential-gene-expression-profiling-of-plucked-hair-follicles-and-integration-with-genetic-data
#7
Lara M Hochfeld, Andreas Keller, Thomas Anhalt, Nadine Fricker, Markus M Nöthen, Stefanie Heilmann-Heimbach
No abstract text is available yet for this article.
July 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30009829/keratinocyte-cytokine-networks-associated-with-human-melanocytic-nevus-development
#8
Arash Chitsazan, Pamela Mukhopadhyay, Blake Ferguson, Herlina Y Handoko, Graeme J Walker
Melanocytes can group together in nevi, commonly thought to form due to intrinsic somatic mutations involving MAPK pathway activation. However, the role of the microenvironment, in particular keratinocytes, in nevogenesis, is rarely studied. Melanocytes proliferate during the hair follicle growth phase and in some basal cell carcinomas, allowing us to construct keratinocyte gene expression clusters correlated with melanocyte activation. We asked whether such correlations are evident in the more subtle context of regulation of melanocyte behaviour in normal skin...
July 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30009827/enamel-anomalies-in-a-pachyonychia-congenita-patient-with-a-mutation-in-krt16
#9
Olivier Duverger, Michael A Cross, Frances J D Smith, Maria I Morasso
Pachyonychia congenita (PC) is a cutaneous disorder caused by a mutation in the KRT6A, KRT6B, KRT6C, KRT16 or KRT17 genes that encode a subset of epithelial keratins. The main features of the disease are painful palmoplantar keratoderma and variable nail dystrophy. In a recent study, we reported that these keratins are incorporated into mature enamel. Moreover, genetic association study showed that common polymorphisms in KRT6A, KRT6B and KRT6C are associated with increased susceptibility to tooth decay. Here we report enamel defects in a PC patient with KRT16 c...
July 13, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30009832/cornulin-is-induced-in-psoriasis-lesions-and-promotes-keratinocyte-proliferation-via-pi3k-akt-pathways
#10
Changji Li, Lei Xiao, Jinjing Jia, Fan Li, Xin Wang, Qiqi Duan, Huiling Jing, Peiwen Yang, Caifeng Chen, Qiong Wang, Jiankang Liu, Yongping Shao, Nanping Wang, Yan Zheng
Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. Cornulin (CRNN) is a major component of the cornified cell envelope and implicated in several epithelial malignancies. Here, we show that CRNN expression was increased in the lesioned epidermis from the patients with psoriasis vulgaris and the skin lesions from the imiquimod (IMQ)-treated mice. Expression of CRNN in cultured keratinocytes (HEKa and HaCaT) was also induced by M5, a mixture of 5 pro-inflammatory cytokines including IL-17Α, IL-22, IL-1α, Oncostatin M and TNF-α...
July 12, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/30009828/cockayne-syndrome-type-a-csa-protein-protects-primary-human-keratinocytes-from-senescence
#11
Sonia Cordisco, Lavinia Tinaburri, Massimo Teson, Donata Orioli, Romilda Cardin, Paolo Degan, Miria Stefanini, Giovanna Zambruno, Liliana Guerra, Elena Dellambra
Defects in Cockayne syndrome type A (CSA), a gene involved in nucleotide excision repair, cause an autosomal recessive syndrome characterized by growth failure, progressive neurological dysfunction, premature aging, and skin photosensitivity and atrophy. Beyond its role in DNA repair, the CSA protein has additional functions in transcription and oxidative stress response, which are not yet fully elucidated. Here, we investigated the role of CSA protein in primary human keratinocyte senescence. Primary keratinocytes from three CS-A patients displayed premature aging features, namely premature clonal conversion, high steady-state levels of ROS and 8-OH-hydroxyguanine (8-OH-Gua) and senescence-associated secretory phenotype (SASP)...
July 12, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29990471/transdifferentiation-of-melanoma-cells-by-the-reprogramming-factors-attenuates-malignant-nature-in-vitro-and-in-vivo
#12
Mikiro Takaishi, Shigetoshi Sano
No abstract text is available yet for this article.
July 7, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29981755/an-integrated-data-resource-for-genomic-analysis-of-cutaneous-t-cell-lymphoma
#13
Li-Wei Chang, Christina Chung Patrone, Wei Yang, Raquel Rabionet, Fernando Gallardo, Blanca Espinet, Mukesh K Sharma, Michael Girardi, Cornelis P Tensen, Maarten Vermeer, Larisa J Geskin
No abstract text is available yet for this article.
July 5, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29964034/eosinophils-determine-dermal-thickening-and-water-loss-in-a-mc903-model-of-atopic-dermatitis
#14
Karmella Naidoo, Ferdinand Jagot, Lieke van den Elsen, Christophe Pellefigues, Angela Jones, Huijun Luo, Karen Johnston, Gavin Painter, Ben Roediger, James Lee, Wolfgang Weninger, Graham Le Gros, Elizabeth Forbes-Blom
Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It has been a difficult disease to treat due to the wide spectrum of clinical manifestations. As such, the current clinical management strategies are non-specific. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch and immune dysregulation. However, the precise role played by effector cells and cytokines have not been fully elucidated...
June 28, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29964033/detection-of-hpv-e7-transcription-at-single-cell-resolution-in-epidermis
#15
S W Lukowski, Z K Tuong, K Noske, A Senabouth, Q H Nguyen, S B Andersen, H P Soyer, I H Frazer, J E Powell
Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA-sequencing (scRNA-seq) may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted scRNA-seq on keratinocytes from a mouse transgenic for the E7 gene of HPV16, and showed sensitive and specific detection of HPV16-E7 mRNA, predominantly in basal keratinocytes...
June 28, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29964032/the-anti-inflammatory-activities-of-propionibacterium-acnes-camp-factor-targeted-acne-vaccines
#16
Yanhan Wang, Tissa R Hata, Yun Larry Tong, Ming-Shan Kao, Christos C Zouboulis, Richard L Gallo, Chun-Ming Huang
Inflammatory acne vulgaris afflicts hundreds of millions of people globally. Propionibacterium acnes (P. acnes), an opportunistic skin bacterium, has been linked to the pathogenesis of acne vulgaris. Our result reveals that a secretory Christie-Atkins-Munch-Peterson (CAMP) factor of P. acnes is up-regulated in anaerobic cultures. Mutation of CAMP factor significantly diminishes the P. acnes colonization and inflammation in mice, demonstrating the essential role of CAMP factor in the cytotoxicity of P. acnes...
June 28, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29959907/pyruvate-protects-against-cellular-senescence-through-the-control-of-mitochondrial-and-lysosomal-function-in-dermal-fibroblasts
#17
Jeong Yeon Kim, Sung Hoon Lee, Il-Hong Bae, Dong Wook Shin, Daejin Min, Mira Ham, Kyu-Han Kim, Tae Ryong Lee, Hyoung-June Kim, Eui Dong Son, Ai-Yong Lee, Yeong Wook Song, In Sup Kil
Mitochondrial dysfunction can drive cellular senescence, which is accompanied by changes in metabolism and increases in senescence-associated secretory phenotypes (SASP). Although pyruvate, a key metabolite for numerous aspects of metabolism, has been used as general supplement in synthetic media, the physiological function of pyruvate underlying its protective role against cellular senescence under normal conditions has remained unknown. Here, we show that extracellular pyruvate prevents senescence in normal human dermal fibroblasts (NHDFs) through increasing the generation of NAD+ during the conversion to lactate...
June 27, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29959906/women-with-hidradenitis-suppurativa-have-an-elevated-risk-of-suicide
#18
Hannu Tiri, Laura Huilaja, Jari Jokelainen, Markku Timonen, Kaisa Tasanen
No abstract text is available yet for this article.
June 27, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29758285/filaggrin-2-deficiency-results-in-abnormal-cell-cell-adhesion-in-the-cornified-cell-layers-and-causes-peeling-skin-syndrome-type-a
#19
Janan Mohamad, Ofer Sarig, Lisa M Godsel, Alon Peled, Natalia Malchin, Ron Bochner, Dan Vodo, Tom Rabinowitz, Mor Pavlovsky, Shahar Taiber, Maya Fried, Marina Eskin-Schwartz, Siwar Assi, Noam Shomron, Jouni Uitto, Jennifer L Koetsier, Reuven Bergman, Kathleen J Green, Eli Sprecher
Peeling skin syndromes form a large and heterogeneous group of inherited disorders characterized by superficial detachment of the epidermal cornified cell layers, often associated with inflammatory features. Here we report on a consanguineous family featuring noninflammatory peeling of the skin exacerbated by exposure to heat and mechanical stress. Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the disease phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis...
June 26, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29935208/laser-irradiation-of-organic-tattoo-pigments-releases-carcinogens-with-3-3-dichlorobenzidine-inducing-dna-strand-breaks-in-human-skin-cells
#20
Henrik Hering, Anja Yu Sung, Nadine Röder, Christoph Hutzler, Hans-Peter Berlien, Peter Laux, Andreas Luch, Ines Schreiver
No abstract text is available yet for this article.
June 20, 2018: Journal of Investigative Dermatology
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