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https://www.readbyqxmd.com/read/28081250/cutaneous-deficiency-of-filaggrin-and-stat3-exacerbates-vaccinia-disease-in-vivo
#1
Yong He, Ishrat Sultana, Kazuyo Takeda, Jennifer L Reed
RATIONALE: Defects in filaggrin and STAT3 are associated with atopic dermatitis (AD) and susceptibility to severe skin infection. METHODS: We evaluated skin infection with the current smallpox vaccine, ACAM-2000, in immunosuppressed mice with combined cutaneous deficiency in filaggrin and STAT3. In parallel, early events post-infection with ACAM-2000 were investigated in cultured keratinocytes in which filaggrin expression was knocked down via siRNA. RESULTS: Immunosuppressed, filaggrin-deficient mice, treated with the topical STAT3 inhibitor Stattic® prior to ACAM-2000 infection, demonstrated rapid weight loss, prolonged vaccinia burden in skin, and dermatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28079852/ichthyosiform-sarcoidosis-report-of-three-cases-from-japan-and-literature-review
#2
Takako Miura, Yasunobu Kato, Toshiyuki Yamamoto
Cutaneous lesions of sarcoidosis present with various manifestations including specific and non-specific cutaneous lesions. Ichthyosiform sarcoidosis is a rare form of cutaneous sarcoidosis, presenting with asymptomatic, adherent, polygonal scales, mainly appearing on the lower limbs.  Ichthyosiform sarcoidosis has a predilection for dark-skinned races, and cases affecting Japanese patients have rarely been reported in English literature.  We herein describe three Japanese cases of ichthyosiform sarcoidosis on the lower limbs...
December 23, 2016: Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG
https://www.readbyqxmd.com/read/28077068/structure-and-evolution-of-the-filaggrin-gene-repeated-region-in-primates
#3
Vanessa Romero, Kazuyoshi Hosomichi, Hirofumi Nakaoka, Hiroki Shibata, Ituro Inoue
BACKGROUND: The evolutionary dynamics of repeat sequences is quite complex, with some duplicates never having differentiated from each other. Two models can explain the complex evolutionary process for repeated genes-concerted and birth-and-death, of which the latter is driven by duplications maintained by selection. Copy number variations caused by random duplications and losses in repeat regions may modulate molecular pathways and therefore affect phenotypic characteristics in a population, resulting in individuals that are able to adapt to new environments...
January 11, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28068897/neotenic-phenomenon-in-gene-expression-in-the-skin-of-foxn1-deficient-nude-mice-a-projection-for-regenerative-skin-wound-healing
#4
Anna Kur-Piotrowska, Marta Kopcewicz, Leslie P Kozak, Pawel Sachadyn, Anna Grabowska, Barbara Gawronska-Kozak
BACKGROUND: Mouse fetuses up to 16 day of embryonic development and nude (Foxn1- deficient) mice are examples of animals that undergo regenerative (scar-free) skin healing. The expression of transcription factor Foxn1 in the epidermis of mouse fetuses begins at embryonic day 16.5 which coincides with the transition point from scar-free to scar-forming skin wound healing. In the present study, we tested the hypothesis that Foxn1 expression in the skin is an essential condition to establish the adult skin phenotype and that Foxn1 inactivity in nude mice keeps skin in the immature stage resembling the phenomena of neoteny...
January 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28057434/atopic-dermatitis-immune-deviation-barrier-dysfunction-ige-autoreactivity-and-new-therapies
#5
REVIEW
Masutaka Furue, Takahito Chiba, Gaku Tsuji, Dugarmaa Ulzii, Makiko Kido-Nakahara, Takeshi Nakahara, Takafumi Kadono
Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD...
January 2, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28002483/physical-characteristics-of-a-citrullinated-pro-filaggrin-epitope-recognized-by-anti-citrullinated-protein-antibodies-in-rheumatoid-arthritis-sera
#6
Nicole Hartwig Trier, Bettina Eide Holm, Ole Slot, Henning Locht, Hanne Lindegaard, Anders Svendsen, Gunnar Houen
Rheumatoid arthritis (RA) is an autoimmune disease of complex etiology. A characteristic feature of a subset of RA is the presence of anti-citrullinated protein antibodies (ACPA), which correlate with a progressive disease course. In this study, we employed streptavidin capture enzyme-linked immunosorbent assay to analyze ACPA reactivity. Using the pro-filaggrin peptide HQCHQEST-Cit-GRSRGRCGRSGS, as template, we analyzed the reactivity of RA sera and healthy donor sera to various peptides in order to determine the physical characteristics of the citrullinated pro-filaggrin epitope and to examine whether biotin labelling influence antibody recognition...
2016: PloS One
https://www.readbyqxmd.com/read/28000306/filaggrin-gene-mutations-and-the-distribution-of-filaggrin-in-oral-mucosa-of-patients-with-oral-lichen-planus-and-healthy-controls
#7
K R Larsen, J D Johansen, J Reibel, C Zachariae, K Rosing, A M L Pedersen
BACKGROUND: Lichen planus (LP) is a chronic inflammatory disease of unknown etiology affecting the skin and oral mucosa. Oral lichenoid lesions (OLL), like oral contact reactions, may resemble oral lichen planus (OLP) both clinically and histopathologically. As OLP and OLL are hyperkeratotic diseases and filaggrin is essential to keratinization the distribution of filaggrin may be altered in these lesions. OBJECTIVES: To investigate if patients with OLP/OLL have 1) altered distribution of filaggrin in the oral mucosa, 2) a higher incidence of mutations in the filaggrin gene (FLG) and 3) active dermatoses, apart from cutaneous LP, than healthy controls; and 4) patients with OLP/OLL and a defect in the FLG have more widespread oral lesions and report more symptoms than OLP/OLL patients without a concomitant defect in the FLG...
December 21, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27995642/health-related-quality-of-life-in-adult-dermatitis-patients-stratified-by-filaggrin-genotype
#8
Nina G Heede, Jacob P Thyssen, Betina H Thuesen, Allan Linneberg, Pal B Szecsi, Steen Stender, Jeanne D Johansen
BACKGROUND: Information concerning health-related quality of life (HRQoL) and comorbidities of adult dermatitis patients stratified by loss-of-function mutations in the filaggrin gene (FLG) is limited. OBJECTIVE: To investigate HRQoL, skin symptoms and comorbidities in adult FLG mutation carriers. METHODS: This cross-sectional study included patients diagnosed with atopic dermatitis and/or hand eczema (n = 520). Patients completed questionnaires about dermatitis, skin symptoms, HRQoL, and comorbidities, including actinic keratosis, and atopic and mental disorders...
December 20, 2016: Contact Dermatitis
https://www.readbyqxmd.com/read/27982552/profile-of-skin-barrier-proteins-and-cytokines-in-adults-with-atopic-dermatitis
#9
Raquel L Orfali, Mariana Colombini Zaniboni, Valeria Aoki
Atopic dermatitis, an inflammatory skin disorder with chronic course and characterized by intense pruritus, is a dermatosis of high prevalence of childhood. However, persistence of the disease in adolescents and adults may occur, and more studies regarding the interactions of the complex triggering factors, especially between the adaptive and innate immune alterations and skin barrier defects are needed. In this review the authors summarize the major novel findings of a dysfunctional skin barrier in AD, with emphasis on tight junction components, such as claudins and on proteins of the keratinocyte differentiation, such as filaggrin...
December 16, 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/27967302/cutaneous-exposure-to-clinically-relevant-pigeon-pea-cajanus-cajan-proteins-promote-th2-dependent-sensitization-and-ige-mediated-anaphylaxis-in-balb-c-mice
#10
Rinkesh Kumar Gupta, Sandeep Kumar, Kriti Gupta, Akanksha Sharma, Ruchi Roy, Alok Kumar Verma, Bhushan P Chaudhari, Mukul Das, Irfan Ahmad Ansari, Premendra D Dwivedi
Epicutaneous (EC) sensitization to food allergens may occur when the skin has been lightly damaged. The study here tested whether cutaneous exposure to pigeon pea protein(s) may cause allergic sensitization. BALB/c mice were either orally gavaged or epicutaneously sensitized by repeated application of pigeon pea crude protein extract (CPE) on undamaged areas of skin without any adjuvant; afterwards, both groups were orally challenged with the pigeon pea CPE. Anaphylactic symptoms along with measures of body temperature, MCPT-1, TSLP, pigeon pea-specific IgE and IgG1, myeloperoxidase (MPO) activity, TH2 cytokines, TH2 transcription factors (TFs) and filaggrin expression were determined...
November 2016: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/27913303/a-mechanistic-target-of-rapamycin-complex-1-2-mtorc1-v-akt-murine-thymoma-viral-oncogene-homolog-1-akt1-cathepsin-h-axis-controls-filaggrin-expression-and-processing-in-skin-a-novel-mechanism-for-skin-barrier-disruption-in-patients-with-atopic-dermatitis
#11
Aishath S Naeem, Cristina Tommasi, Christian Cole, Stuart J Brown, Yanan Zhu, Benjamin Way, Saffron A G Willis Owen, Miriam Moffatt, William O Cookson, John I Harper, Wei-Li Di, Sara J Brown, Thomas Reinheckel, Ryan F L O'Shaughnessy
BACKGROUND: Filaggrin, which is encoded by the filaggrin gene (FLG), is an important component of the skin's barrier to the external environment, and genetic defects in FLG strongly associate with atopic dermatitis (AD). However, not all patients with AD have FLG mutations. OBJECTIVE: We hypothesized that these patients might possess other defects in filaggrin expression and processing contributing to barrier disruption and AD, and therefore we present novel therapeutic targets for this disease...
November 29, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27902816/association-of-filaggrin-loss-of-function-and-thymic-stromal-lymphopoietin-variation-with-treatment-use-in-pediatric-atopic-dermatitis
#12
Joshua Chang, Nandita Mitra, Ole Hoffstad, David J Margolis
Importance: Atopic dermatitis (AD) is a common illness of childhood. Objective: To determine whether variations in FLG and TSLP genotype corresponded to differences in treatment use over time. Design, Setting, and Participants: This prospective cohort study recruited and followed a volunteer sample of 842 children enrolled in the Pediatric Eczema Elective Registry who provided saliva samples for DNA extraction for 10 years. Eligibility criteria included age 2 to 17 years, AD diagnosis without cancer, and prior pimecrolimus use...
November 30, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27868148/the-alarmins-hmbg1-and-il-33-downregulate-structural-skin-barrier-proteins-and-impair-epidermal-growth
#13
Uffe Nygaard, Ellen H van den Bogaard, Hanna Niehues, Malene Hvid, Mette Deleuran, Claus Johansen, Christian Vestergaard
The epidermal-derived "alarmins" high-mobility group box 1 (HMGB1) protein and interleukin-33 (IL-33) are upregulated in patients with atopic dermatitis. However, their capacity as pro-inflammatory cytokines and their derived effects on skin barrier regulation are poorly elucidated. We investigated the impact of HMGB1 and IL-33 on gene transcription, protein expression and epidermal differentiation across 3 distinct keratinocyte in vitro models. Primary keratinocytes from healthy donors were used in submerged monolayer cultures, 3D human epidermis equivalents and 3D human skin equivalents...
October 14, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27833999/methyl-%C3%AE-cyclodextrin-treatment-combined-to-incubation-with-interleukin-4-reproduces-major-features-of-atopic-dermatitis-in-a-3d-culture-model
#14
Tatiana do Nascimento Pedrosa, Evelyne De Vuyst, Abdallah Mound, Catherine Lambert de Rouvroit, Silvya Stuchi Maria-Engler, Yves Poumay
Atopic dermatitis (AD) skin is characterized by over-expression of interleukin (IL)-4, IL-13 and IL-25. When methyl-β-cyclodextrin (MβCD) treatment preceded exposure to these interleukins, combination of both treatments was found to mimic hallmarks of AD in vitro, such as barrier weakening, histological alterations and typical signaling responses in a reconstructed human epidermis (RHE). However, the respective role of each IL and whether any of them is critical when combined with MβCD treatment was unknown...
January 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/27828771/how-does-chronic-cigarette-smoke-exposure-affect-human-skin-a-global-proteomics-study-in-primary-human-keratinocytes
#15
Pavithra Rajagopalan, Vishalakshi Nanjappa, Remya Raja, Ankit P Jain, Kiran K Mangalaparthi, Gajanan J Sathe, Niraj Babu, Krishna Patel, Nükhet Cavusoglu, Jeremie Soeur, Akhilesh Pandey, Nita Roy, Lionel Breton, Aditi Chatterjee, Namita Misra, Harsha Gowda
Cigarette smoking has been associated with multiple negative effects on human skin. Long-term physiological effects of cigarette smoke are through chronic and not acute exposure. Molecular alterations due to chronic exposure to cigarette smoke remain unclear. Primary human skin keratinocytes chronically exposed to cigarette smoke condensate (CSC) showed a decreased wound-healing capacity with an increased expression of NRF2 and MMP9. Using quantitative proteomics, we identified 4728 proteins, of which 105 proteins were overexpressed (≥2-fold) and 41 proteins were downregulated (≤2-fold) in primary skin keratinocytes chronically exposed to CSC...
November 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27824549/acpas-are-much-more-than-diagnostic-autoantibodies
#16
REVIEW
Abdulla Watad, Howard Amital
Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation...
October 31, 2016: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/27818314/pax6-regulates-human-corneal-epithelium-cell-identity
#17
Koji Kitazawa, Takafusa Hikichi, Takahiro Nakamura, Chie Sotozono, Shigeru Kinoshita, Shinji Masui
PAX6, a paired box transcription factor, is necessary for eye development. However, how it regulates the cell identity of human corneal epithelial cells (CECs) is not well understood. We aimed to clarify the function of PAX6 in human CECs using gene knockout via the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) system. We designed guide RNAs for different targets in PAX6. PAX6-depleted CECs maintained the epithelial morphology, but became larger. Global analyses using microarray revealed that down-regulated genes were primarily CEC-specific and included keratin 12, keratin 3, clusterin (CLU), aldehyde dehydrogenase 3 family member A1 (ALDH3A1), angiopoietin-like 7 (ANGPTL7) and transketolase (TKT), while up-regulated genes were primarily epidermis-related and included keratin 10, keratin 1, involucrin (IVL), filaggrin (FLG)...
November 3, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27813070/atopic-dermatitis-a-tale-of-two-distinct-pathomechanisms-that-make-you-itch
#18
Edward F Knol, DirkJan Hijnen
Atopic dermatitis (AD) or eczema is the most common chronic inflammatory skin disease. It is a multifactorial disease with local and systemic immune changes. Current therapies focus on restoring the local skin barrier or inhibiting immune responses. In this issue of the European Journal of Immunology, Sehra et al. [Eur. J. Immunol. 2016. 46:2609-2613] describe a mouse model with T-cell-specific expression of constitutively active Stat6 in Flaky tail mice, which have mutations in the Flg and Tmem79 genes. The authors describe that it is the combination of changes in the skin barrier proteins filaggrin and Tmem79, together with Th2 cytokine signaling in the constitutively active Stat6 transgene, that drives the immune-pathomechanism in AD...
November 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27805415/determination-of-natural-moisturizing-factors-in-the-skin-raman-microspectroscopy-versus-hplc
#19
S A Koppes, P Kemperman, I van Tilburg, F Calkoen-Kwa, K A Engebretsen, G J Puppels, P J Caspers, S Kezic
BACKGROUND: Natural moisturizing factors (NMF) is used as genotypic and phenotypic biomarker in diagnostics. This study is a side-to-side comparison of two different methods to determine NMF in atopic dermatitis patients: Raman microspectroscopy and stratum corneum tape stripping followed by HPLC. RESULTS: Measured NMF values were significantly correlated (R2 = 0.61; P < 0.0001), both methods demonstrated a concentration-depth dependence of NMF and reduced NMF levels in the carriers of filaggrin null mutations...
November 2, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27793761/alterations-in-epidermal-eicosanoid-metabolism-contribute-to-inflammation-and-impaired-late-differentiation-in-flg-mutated-atopic-dermatitis
#20
Stefan Blunder, Ralph Rühl, Verena Moosbrugger-Martinz, Christine Krimmel, Anita Geisler, Huiting Zhu, Debra Crumrine, Peter M Elias, Robert Gruber, Matthias Schmuth, Sandrine Dubrac
Loss-of-function mutations in the FLG gene cause ichthyosis vulgaris (IV) and represent the major predisposing genetic risk factor for atopic dermatitis (AD). Although both conditions are characterized by epidermal barrier impairment, AD also exhibits signs of inflammation. This work was aimed at delineating the role of FLG loss-of-function mutations on eicosanoid metabolism in IV and AD. Using human epidermal equivalents (HEEs) generated with keratinocytes isolated from nonlesional skin of patients with FLG wild-type AD (WT/WT), FLG-mutated AD (FLG/WT), IV (FLG/FLG), or FLG WT control skin, we assessed the potential autocrine role of epidermal-derived eicosanoids in FLG-associated versus FLG-WT AD pathogenesis...
October 26, 2016: Journal of Investigative Dermatology
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