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Chiung-Yueh Hsu, Géraldine Gasc, Anne-Aurélie Raymond, Odile Burlet-Schiltz, Hidenari Takahara, Guy Serre, Marie-Claire Méchin, Michel Simon
Hornerin (HRNR) shares numerous features with filaggrin, a key contributor to the epidermal barrier functions. The two proteins display a related structural organization, are expressed by the granular keratinocytes as a large precursor processed by proteolysis, and are cross-linked to the cornified cell envelopes. Two main steps in the metabolism of filaggrin are its deimination and calpain-1 cleavage. Here, using ion-exchange chromatography and two-dimensional gel electrophoresis of human epidermis extracts, we determined that HRNR is deiminated in vivo...
October 11, 2016: Journal of Investigative Dermatology
Hanna Niehues, Joost Schalkwijk, Ivonne M J J van Vlijmen-Willems, Diana Rodijk-Olthuis, Michelle M van Rossum, Ewa Wladykowski, Johanna M Brandner, Ellen H J van den Bogaard, Patrick L J M Zeeuwen
We investigated differentiation and barrier properties of epidermal equivalents derived from ichthyosis vulgaris keratinocytes that were homozygous for FLG null mutations. We found no effect on penetration of tracer molecules, compared with filaggrin proficient keratinocytes.
October 11, 2016: Journal of Allergy and Clinical Immunology
Susanne Stemmler, Sabine Hoffjan
Atopic dermatitis (AD) is a common and complex skin disease associated with both genetic and environmental factors. Loss-of-function mutations in the filaggrin gene, encoding a structural protein with an important role in epidermal barrier function, constitutes a well recognised susceptibility locus for AD. Further, genome-wide association studies (GWAS), including large meta-analyses, have discovered 38 additional susceptibility loci with genome-wide significance. However, the reported variations only explain a fraction of the overall heritability of AD...
October 7, 2016: Molecular and Cellular Probes
Patrick L J M Zeeuwen, Thomas H A Ederveen, Danique A van der Krieken, Hanna Niehues, Jos Boekhorst, Sanja Kezic, Daniëlle A T Hanssen, Marisol E Otero, Ivonne M J J van Vlijmen-Willems, Diana Rodijk-Olthuis, Denise Falcone, Ellen H J van den Bogaard, Marijke Kamsteeg, Heleen D de Koning, Manon E J Zeeuwen-Franssen, Maurice A M van Steensel, Michiel Kleerebezem, Harro M Timmerman, Sacha A F T van Hijum, Joost Schalkwijk
Mutations in the filaggrin gene, which cause the skin disease ichthyosis vulgaris and are a genetic risk factor for atopic dermatitis, alter the cutaneous microbiome thereby affecting keratinocyte host defense responses following skin barrier disruption.
October 7, 2016: Journal of Allergy and Clinical Immunology
Yuangang Liu, Zhiping Wang, Rachel De La Torre, Ashley Barling, Takahiro Tsujikawa, Noah Hornick, Jon Hanifin, Eric Simpson, Yun Wang, Emily Swanzey, Aaron Wortham, Hao Ding, Lisa M Coussens, Molly Kulesz-Martin
Altered innate immunity is a feature of certain skin inflammatory diseases such as psoriasis and atopic dermatitis (AD). In this study, we provide evidence that deficiency in Trim32 (a tripartite motif (TRIM) protein with innate antiviral activity) contributes to a Th2 biased response and predisposes to features of AD in mice. Upon treatment with the TLR7 agonist imquimod (IMQ), Trim32 knockout (KO) mice displayed compromised psoriasiform phenotypes and defective Th17 response. Instead, IMQ treatment of Trim32 KO mice induced AD-like phenotypes with enhanced skin infiltration of eosinophils and mast cells, elevation of Th2 cytokines/chemokines expression, and reduced expression of filaggrin protein expression...
October 5, 2016: Journal of Investigative Dermatology
Muthukrishnan Eaaswarkhanth, Duo Xu, Colin Flanagan, Margarita Rzhetskaya, M Geoffrey Hayes, Ran Blekhman, Nina Jablonski, Omer Gokcumen
Human skin has evolved rapidly, leaving evolutionary signatures in the genome. The filaggrin (FLG) gene is widely studied for its skin-barrier function in humans. The extensive genetic variation in this gene, especially common loss-of-function (LoF) mutations, has been established as primary risk factors for atopic dermatitis. To investigate the evolution of this gene, we analyzed 2,504 human genomes and genotyped the copy number variation of filaggrin repeats within FLG in 126 individuals from diverse ancestral backgrounds...
September 27, 2016: Genome Biology and Evolution
Ekaterini Politi, Aspasia Angelakopoulou, Dimitra Grapsa, Maria Zande, Kalliopi Stefanaki, Ioanna Panagiotou, Eleftheria Roma, Ekaterini Syrigou
OBJECTIVES: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. METHODS: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with gastroesophageal reflux disease (GERD), and a control group of 14 sex and age-matched healthy children were enrolled...
September 24, 2016: Journal of Pediatric Gastroenterology and Nutrition
Hitokazu Esaki, Patrick M Brunner, Yael Renert-Yuval, Tali Czarnowicki, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Donald B Johnson, Bruce Bauer, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xiangyu Peng, Yeriel D Estrada, Hui Xu, Christina de Guzman Strong, Mayte Suárez-Fariñas, James G Krueger, Amy S Paller, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD...
September 15, 2016: Journal of Allergy and Clinical Immunology
W H I McLean
The main proteinaceous component of the keratohyalin granules within the granular layer keratinocytes of the epidermis is the giant, repetitive polyprotein profilaggrin. When granular layer cells commit to terminal differentiation to form the flattened squames of the stratum corneum, profilaggrin is rapidly cleaved into multiple copies of the 37 kDa filaggrin monomer, which binds to and condenses the keratin cytoskeleton, thereby facilitating cellular compression. Within the stratum corneum, filaggrin is broken down to form natural moisturising factor, a pool of amino acids and derivatives thereof that exerts multiple effects...
October 2016: British Journal of Dermatology
Sunil K Ahuja, Muthu Saravanan Manoharan, Nathan L Harper, Fabio Jimenez, Benjamin D Hobson, Hernan Martinez, Puraskar Ingale, Ya-Guang Liu, Andrew Carrillo, Zheng Lou, Dean L Kellog, Seema S Ahuja, Cynthia G Rather, Robert E Esch, Daniel A Ramirez, Robert A Clark, Kari Nadeau, Charles P Andrews, Robert L Jacobs, Weijing He
BACKGROUND: An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis (AR), relates to an intact epithelial/epidermal barrier during early childhood. Conceivably, the immunologic and genomic footprint of this resistance is preserved in nonatopic, nonallergic adults and is unmasked during exposure to an aeroallergen. OBJECTIVE: To obtain direct support of the epithelial/epidermal barrier model for AR...
September 19, 2016: Journal of Allergy and Clinical Immunology
Y Tokura
No abstract text is available yet for this article.
October 2016: British Journal of Dermatology
In Jun Yang, Dong-Ung Lee, Heung Mook Shin
Valencene (VAL) isolated from Cyperus rotundus possesses various biological effects such as antiallergic and antimelanogenesis activity. We investigated the effect of VAL on atopic dermatitis (AD) skin lesions and their molecular mechanisms. We topically applied VAL to 1-chloro-2,4-dinitrobenzene (DNCB) sensitized NC/Nga mice. Modified scoring atopic dermatitis index, scratching behavior, and histological/immunohistochemical staining were used to monitor disease severity. RT-PCR, western blotting, and enzyme-linked immunosorbent assay were used to determine the level of IgE, proinflammatory cytokines/chemokines production, and skin barrier proteins expression...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Zeinab Ghanavati, Mahmoud Orazizadeh, Vahid Bayati, Mohammad Reza Abbaspour, Layasadat Khorsandi, Esrafil Mansouri, Niloofar Neisi
OBJECTIVE: The organotypic co-culture is a well-known technique to examine cellular interactions and their roles in stem cell proliferation and differentiation. This study aims to evaluate the effects of dermal fibroblasts (DFs) on epidermal differentiation of adipose-derived stem cells (ASCs) using a three-dimensional (3D) organotypic co- culture technique. MATERIALS AND METHODS: In this experimental research study, rat DFs and ASCs were isolated and cultured separately on electrospun polycaprolactone (PCL) matrices...
2016: Cell Journal
Pawinee Rerknimitr, Hideaki Tanizaki, Yasuo Yamamoto, Wataru Amano, Saeko Nakajima, Chisa Nakashima, Yumi Nonomura, Jade Wititsuwannakul, Yoshiki Miyachi, Atsushi Otsuka, Kenji Kabashima
No abstract text is available yet for this article.
August 31, 2016: Journal of Investigative Dermatology
Mio Matsui, Kosuke Tanaka, Naoki Higashiguchi, Hisato Okawa, Yoichi Yamada, Ken Tanaka, Soichiro Taira, Tomoko Aoyama, Misaki Takanishi, Chika Natsume, Yuuki Takakura, Norihisa Fujita, Takeshi Hashimoto, Takashi Fujita
Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity...
September 2016: Journal of Pharmacological Sciences
Takuo Yuki, Megumi Tobiishi, Ayumi Kusaka-Kikushima, Yukiko Ota, Yoshiki Tokura
Tight junction (TJ) dysfunction in the stratum granulosum leads to aberrant barrier function of the stratum corneum (SC) in the epidermis. However, it is unclear whether TJs are perturbed in atopic dermatitis (AD), a representative aberrant SC-related skin disease, and whether some factors related to AD pathogenesis induce TJ dysfunction. To address these issues, we investigated the alterations of TJs in AD skin and the effects of Th2 and Th17 cytokines on TJs in a skin-equivalent model. The levels of TJ proteins were determined in the epidermis of nonlesional and lesional skin sites of AD...
2016: PloS One
S Asad, M C G Winge, C-F Wahlgren, K D Bilcha, M Nordenskjöld, F Taylan, M Bradley
BACKGROUND: The strong association between epidermal barrier gene variants and Atopic Dermatitis (AD) highlights that impaired skin barrier is a key feature in the pathogenesis of AD. Although the filaggrin (FLG) gene is the major AD risk gene in European and Asian populations, disease-associated variants remain elusive in African populations. OBJECTIVE: A previous study has reported that variants in the tight junction gene CLDN1 have been associated with AD susceptibility and disease severity in African-Americans...
August 31, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Mariana Colombini Zaniboni, Luciana Paula Samorano, Raquel Leão Orfali, Valéria Aoki
Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system...
July 2016: Anais Brasileiros de Dermatologia
Xiaojing Kuang, Lingling Sun, Shuzhen Liu, Zhenzhen Zhao, Danrui Zhao, Song Liu, Bing Luo
The relationship between the Filaggrin gene (FLG) rs2065955 polymorphism and susceptibility to Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) was investigated in Shandong Province, China. We detected the FLG rs2065955 genotype and allele distribution by using PCR and restriction fragment length polymorphism (RFLP) in 64 EBVaGC, 82 EBVnGC, and 111 normal control samples. Immunohistochemistry was used to detect the level of FLG protein in 35 EBVaGC and 51 EBVnGC tumor tissues...
August 2016: Virologica Sinica
Alan D Irvine, Lawrence F Eichenfield, Sheila F Friedlander, Eric L Simpson
About a decade age, loss-of-function mutations in the filaggrin molecule were first implicated in the pathogenesis of ichthyosis vulgaris and, subsequently, of atopic dermatitis and other atopic diseases. Since then, intensive study of the role of filaggrin null mutations have led to other milestones in understanding the pathologic pathways in these diseases, including the initiation, maintenance, and promotion of the disease processes. The result has been new and emerging clinical and pharmacologic strategies for early identification of and intervention in atopic diseases...
June 2016: Seminars in Cutaneous Medicine and Surgery
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