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Journal of Investigative Dermatology

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https://www.readbyqxmd.com/read/28642156/tgf%C3%AE-smad-microrna-486-3p-signaling-axis-mediates-keratin-17-expression-and-keratinocyte-hyperproliferation-in-psoriasis
#1
Man Jiang, Zhongbin Sun, Erle Dang, Bing Li, Hui Fang, Junqin Li, Lin Gao, Kaiming Zhang, Gang Wang
Keratin 17 (K17) is strongly expressed in psoriatic lesions but not healthy skin, and plays a crucial role in disease pathogenesis. The mechanism of aberrant K17 expression in psoriasis has not been fully elucidated. MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play important roles in regulating gene expression. Psoriasis exhibits a specific miRNA expression profile distinct from that of healthy skin. In this study, we showed that miR-486-3p was markedly reduced in psoriatic epidermis and negatively correlated with the psoriasis area and severity index (PASI) score...
June 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634035/psoriasis-associated-late-cornified-envelope-lce-proteins-have-antibacterial-activity
#2
Hanna Niehues, Lam C Tsoi, Danique A van der Krieken, Patrick A M Jansen, Merel A W Oortveld, Diana Rodijk-Olthuis, Ivonne M J J van Vlijmen, Wiljan J A J Hendriks, Richard W Helder, Joke A Bouwstra, Ellen H van den Bogaard, Philip E Stuart, Rajan P Nair, James T Elder, Patrick L J M Zeeuwen, Joost Schalkwijk
Terminally differentiating epidermal keratinocytes express a large number of structural and antimicrobial proteins that are involved in the physical barrier function of the stratum corneum and provide innate cutaneous host defense. Late cornified envelope (LCE) genes, located in the epidermal differentiation complex on chromosome 1, encode a family of 18 proteins of unknown function, whose expression is largely restricted to epidermis. Deletion of two members, LCE3B and LCE3C (LCE3B/C-del), is a widely replicated psoriasis risk factor that interacts with the major psoriasis-psoriasis risk gene HLA-C*06...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#3
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634033/nickel-sulfate-promotes-il-17a-producing-cd4-t-cells-by-an-il-23-dependent-mechanism-regulated-by-tlr4-and-jak-stat-pathways
#4
Rami Bechara, Diane Antonios, Hayat Azouri, Marc Pallardy
Allergic contact dermatitis, caused by nickel, is a delayed-type hypersensitivity reaction and 14.5% of the general population may be affected in Europe. Among a wide range of cytokines, the IL-12 family has unique structural and immunological characteristics. While IL-12p70 promotes T helper (Th) 1 cells polarization, IL-23 promotes Th17 cells development and both have been isolated from nickel-allergic patients. In this work, we were interested in understanding the mechanism behind nickel-induced Th17 cells development...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634032/ciclosporin-use-in-epidermal-necrolysis-is-associated-with-an-important-mortality-reduction-evidence-from-three-different-approaches
#5
C González-Herrada, S Rodríguez-Martín, L Cachafeiro, V Lerma, O González, J A Lorente, A Rodríguez-Miguel, J González-Ramos, G Roustan, E Ramírez, T Bellón, F J de Abajo
Several immunomodulatory agents are used in the treatment of Epidermal Necrolysis (EN), but evidence of their efficacy is limited. The Autonomous Community of Madrid has two reference Burn Units (BUs) to which all patients with EN are referred to. One BU has mostly used ciclosporin (CsA), while the other has used non-CsA therapies (mainly high-dose intravenous immunoglobulin). The allocation of patients to one or another BU was mainly based on proximity resembling a random assignment. Thus, we took advantage of this "natural experiment" to estimate the mortality risk ratio (MRR) of CsA (N=26) as compared to non-CsA (n=16) using hospital as an instrumental variable (IV) over the period 2001-2015...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28629629/association-between-lithium-use-and-melanoma-risk-and-mortality-a-population-based-study
#6
Maryam M Asgari, Andy J Chien, Ai Lin Tsai, Bruce Fireman, Charles P Quesenberry
Laboratory studies show lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Lithium exposure (n=11,317) was assessed from pharmacy databases, serum lithium levels were obtained from electronic laboratory databases, and incident cutaneous melanomas (n= 14,056) were identified from an established cancer registry...
June 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28625464/becker-s-nevus-and-lethal-beta-actin-mutations
#7
Rudolf Happle
The etiology of Becker's nevus and Becker's nevus syndrome has been until now unknown. Cai et al. provide evidence that these disorders are caused by lethal mutations in ACTB, a gene coding for beta-actin. They hypothesize that these mutations may interfere with Hedgehog pathway signaling. Their findings have important implications for clinical genetics, and they open new aspects in hair research.
June 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28601418/psenen-mutation-carriers-with-co-manifestation-of-acne-inversa-ai-and-dowling-degos-disease-ddd-is-ai-or-ddd-the-subphenotype
#8
Chengrang Li, Wenrui Li, Haoxiang Xu, Xiaofeng Zhang, Bin Su, Wanlu Zhang, Xue Zhang, Baoxi Wang
No abstract text is available yet for this article.
June 7, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28599981/p90rsk-blockade-inhibits-dual-braf-and-mek-inhibitor-resistant-melanoma-by-targeting-protein-synthesis
#9
Nicholas Theodosakis, Goran Micevic, Casey G Langdon, Alessandra Ventura, Robert Means, David F Stern, Marcus W Bosenberg
Despite improvements in survival in metastatic melanoma with combined BRAF and MEK inhibitor treatment, the overwhelming majority of patients eventually acquire resistance to both agents. Consequently, new targets for therapy in resistant tumors are currently being evaluated. Previous studies have identified p90RSK family kinases as key factors for growth and proliferation, as well as protein synthesis via assembly of the m(7)-GTP cap-dependent translation complex. We sought to evaluate inhibitors of p90RSK family members: BI-D1870 and BRD7389, for their ability to inhibit both proliferation and protein synthesis in patient-derived melanoma cell lines with acquired resistance to combined treatment with the BRAF inhibitor vemurafenib and MEK inhibitor selumetinib...
June 6, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28596001/establishing-and-validating-an-ichthyosis-severity-index
#10
Nareh V Marukian, Yanhong Deng, Geliang Gan, Ivy Ren, Wisblaude Thermidor, Brittany G Craiglow, Leonard M Milstone, Keith A Choate
We designed and validated a Visual Index for Ichthyosis Severity (VIIS) for scale and erythema that provides 1) written descriptions of the features characteristic of each level of severity 2) visual standards for 4 body sites, and 3) two distinct standards to account for different types of scale. We tested the VIIS for reliability and reproducibility using two different settings: one that utilized scoring of 60 test photographs by 10 dermatologists, and one with in-person evaluations on 85 subjects by 12 dermatologists at the Foundation for Ichthyosis and Related Skin Types (FIRST) conference...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28596000/the-nrf2-gch1-bh4-axis-ameliorates-radiation-induced-skin-injury-by-modulating-the-ros-cascade
#11
Jiao Xue, Chenxiao Yu, Wenjiong Sheng, Wei Zhu, Judong Luo, Qi Zhang, Hongying Yang, Han Cao, Wenjie Wang, Jundong Zhou, Jinchang Wu, Peng Cao, Ming Chen, Wei-Qun Ding, Jianping Cao, Shuyu Zhang
Radiation-induced skin injury is a common side effect of radiotherapy and can limit the duration and dose of radiotherapy. Most early work focused on elimination of reactive oxygen species (ROS) after radiation, however, less is known about the mechanisms underlying amplification of ROS and consequent skin injury by radiation. 5,6,7,8-tetrahydrobiopterin (BH4) is an essential co-factor for all nitric oxide synthases (NOSs). Inadequate availability of BH4 leads to uncoupling of NOSs and production of highly oxidative radicals...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28595999/p63-transcription-factor-regulates-nuclear-shape-and-expression-of-nuclear-envelope-associated-genes-in-epidermal-keratinocytes
#12
Valentina Rapisarda, Igor Malashchuk, Inemo E Asamaowei, Krzysztof Poterlowicz, Michael Y Fessing, Andrey A Sharov, Iakowos Karakesisoglou, Vladimir A Botchkarev, Andrei Mardaryev
The maintenance of a proper nuclear architecture and 3D organization of the genes, enhancer elements and transcription machinery plays an essential role in tissue development and regeneration. Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by marked decrease in expression of several nuclear envelop-associated components (Lamin B1, Lamin A/C, SUN1, Nesprin-3, Plectin) compared to controls. Furthermore, ChIP-qPCR assay showed enrichment of p63 on Sun1, Syne3 and Plec promoters, suggesting them as p63 targets...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28595998/targeting-of-cxxc5-by-a-competing-peptide-stimulates-hair-re-growth-and-wound-induced-hair-neogenesis
#13
Soung-Hoon Lee, Seol Hwa Seo, Dong-Hwan Lee, Long-Quan Pi, Won-Soo Lee, Kang-Yell Choi
The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair re-growth and wound-induced hair follicle neogenesis (WIHN) via an interaction with Dishevelled (Dvl). CXXC5 was up-regulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28595997/hpv8-field-cancerization-in-a-transgenic-mouse-model-is-due-to-lrig1-keratinocyte-stem-cell-expansion
#14
Simone Lanfredini, Carlotta Olivero, Cinzia Borgogna, Federica Calati, Kathryn Powell, Kelli-Jo Davies, Marco De Andrea, Sarah Harries, Hiu Kwan Carolyn Tang, Herbert Pfister, Marisa Gariglio, Girish K Patel
β-HPV cause near ubiquitous latent skin infection within long-lived hair follicle keratinocyte stem cells (HF KSC). In patients with epidermodysplasia verruciformis (EV), β-HPV viral replication is associated with skin keratosis and cutaneous squamous cell carcinoma (SCC). To determine the role of HF KSC in β-HPV induced skin carcinogenesis, we utilized a transgenic mouse model in which the keratin 14 promoter drives expression of the entire HPV8 early region (HPV8tg). HPV8tg mice developed thicker skin in comparison to wild type littermates consistent with a hyperproliferative epidermis...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28595996/tapinarof-is-a-natural-ahr-agonist-that-resolves-skin-inflammation-in-mice-and-humans
#15
Susan H Smith, Channa Jayawickreme, David J Rickard, Edwige Nicodeme, Thi Bui, Cathy Simmons, Christine M Coquery, Jessica Neil, William M Pryor, David Mayhew, Deepak K Rajpal, Katrina Creech, Sylvia Furst, James Lee, Dalei Wu, Fraydoon Rastinejad, Timothy M Willson, Fabrice Viviani, David C Morris, John T Moore, Javier Cote-Sierra
Tapinarof (GSK2894512) is a naturally derived topical treatment with demonstrated efficacy for psoriasis and atopic dermatitis (AD) patients, although the biologic target and mechanism of action had been unknown. We demonstrate that the anti-inflammatory properties of tapinarof are mediated through activation of the Aryl hydrocarbon Receptor (AhR). We show that tapinarof binds and activates AhR in multiple cell types, including cells of the target tissue -human skin. In addition, tapinarof moderates proinflammatory cytokine expression in stimulated peripheral blood CD4+ T cells and ex vivo human skin, and impacts barrier gene expression in primary human keratinocytes; both of these processes are likely to be downstream of AhR activation based on current evidence...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28595995/mir-146b-probably-assists-mirna-146a-in-the-suppression-of-keratinocyte-proliferation-and-inflammatory-responses-in-psoriasis
#16
Helen Hermann, Toomas Runnel, Alar Aab, Hansjörg Baurecht, Elke Rodriguez, Nathaniel Magilnick, Egon Urgard, Liisi Šahmatova, Ele Prans, Julia Maslovskaja, Kristi Abram, Maire Karelson, Bret Kaldvee, Paula Reemann, Uku Haljasorg, Beate Rückert, Paulina Wawrzyniak, Michael Weichenthal, Ulrich Mrowietz, Andre Franke, Christian Gieger, Jonathan Barker, Richard Trembath, Lam C Tsoi, James T Elder, Eric R Tkaczyk, Kai Kisand, Pärt Peterson, Külli Kingo, Mark Boldin, Stephan Weidinger, Cezmi A Akdis, Ana Rebane
miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In the present study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in lesional skin of psoriasis patients. The expression of miR-146a was about 2-fold higher than that of miR-146b in healthy human skin and it was more strongly induced by stimulation of pro-inflammatory cytokines in keratinocytes and fibroblasts...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28583676/second-international-symposium-epigenetic-regulation-of-skin-regeneration-and-aging-from-chromatin-biology-towards-the-understanding-of-epigenetic-basis-of-skin-diseases
#17
Vladimir A Botchkarev
No abstract text is available yet for this article.
June 2, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28576738/monoallelic-large-intragenic-krt5-deletions-account-for-genetically-unsolved-cases-of-epidermolysis-bullosa-simplex
#18
Cristina Has, Hauke Schumann, Juna Leppert, Yinghong He, Britta Hartmann, Ingrid Hausser, Jürgen Kohlhase
No abstract text is available yet for this article.
May 30, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28576737/nrf2-promotes-keratinocyte-proliferation-in-psoriasis-through-up-regulation-of-keratin-6-keratin-16-and-keratin-17
#19
Luting Yang, Xueli Fan, Tingting Cui, Erle Dang, Gang Wang
Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation of epidermis. Although hyperproliferation-associated keratins K6, K16 and K17 are considered to be the hallmarks of psoriasis, the molecular basis underlying the overexpression of these keratins remains unclear. Nuclear factor erythroid-derived 2 related factor 2 (Nrf2) regulates cell proliferation. Therefore, we investigated whether Nrf2 regulates keratinocyte proliferation via promoting expression of K6, K16 and K17 in psoriasis...
May 30, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28576736/oral-vitamin-d-rapidly-attenuates-inflammation-from-sunburn-an-interventional-study
#20
Jeffrey F Scott, Lopa M Das, Sayeeda Ahsanuddin, Yuqi Qiu, Amy M Binko, Zachary P Traylor, Sara M Debanne, Kevin D Cooper, Rebecca Boxer, Kurt Q Lu
The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, twenty healthy adults were randomized to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of ultraviolet radiation. Compared to placebo, participants receiving vitamin D3 (200,000 IU) demonstrated reduced expression of pro-inflammatory mediators TNF-α (p=0...
May 30, 2017: Journal of Investigative Dermatology
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