Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17

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 t...

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Veröffentlicht in:PloS one 2016-09, Vol.11 (9), p.e0161759-e0161759
Hauptverfasser: Yuki, Takuo, Tobiishi, Megumi, Kusaka-Kikushima, Ayumi, Ota, Yukiko, Tokura, Yoshiki
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Tobiishi, Megumi
Kusaka-Kikushima, Ayumi
Ota, Yukiko
Tokura, Yoshiki
description 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. Western blot and immunohistochemical analyses revealed that the levels of zonula occludens 1 were decreased in the nonlesional sites of AD, and the levels of zonula occludens 1 and claudin-1 were decreased in the lesional sites relative to the levels in skin from healthy subjects. Next, we examined the effects of interleukin (IL)-4, tumor necrosis factor-α, IL-17, and IL-22 on the TJ barrier in a skin-equivalent model. Only IL-17 impaired the TJ barrier. Furthermore, we observed a defect in filaggrin monomer degradation in the IL-17-treated skin model. Thus, TJs are dysfunctional in AD, at least partly, due to the effect of IL-17, which may result in an aberrant SC barrier.
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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. Western blot and immunohistochemical analyses revealed that the levels of zonula occludens 1 were decreased in the nonlesional sites of AD, and the levels of zonula occludens 1 and claudin-1 were decreased in the lesional sites relative to the levels in skin from healthy subjects. Next, we examined the effects of interleukin (IL)-4, tumor necrosis factor-α, IL-17, and IL-22 on the TJ barrier in a skin-equivalent model. Only IL-17 impaired the TJ barrier. 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metabolism</topic><topic>Clostridium perfringens</topic><topic>Cytokines</topic><topic>Dermatitis</topic><topic>Dermatitis, Atopic - metabolism</topic><topic>Dermatitis, Atopic - pathology</topic><topic>Disease</topic><topic>Eczema</topic><topic>Epidermis</topic><topic>Equivalence</topic><topic>Filaggrin</topic><topic>Filaggrin Proteins</topic><topic>Health aspects</topic><topic>Helper cells</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Interleukin 17</topic><topic>Interleukin 22</topic><topic>Interleukin-17 - pharmacology</topic><topic>Interleukin-4 - pharmacology</topic><topic>Interleukins - pharmacology</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>Keratinocytes - pathology</topic><topic>Localization</topic><topic>Lymphocytes T</topic><topic>Medicine and Health Sciences</topic><topic>Membrane proteins</topic><topic>Mutation</topic><topic>Pathogenesis</topic><topic>Pathogens</topic><topic>Physical Sciences</topic><topic>Pneumoviridae</topic><topic>Proteins</topic><topic>Psoriasis</topic><topic>Research and Analysis Methods</topic><topic>Risk factors</topic><topic>Skin</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Skin diseases</topic><topic>Stratum corneum</topic><topic>Tight Junction Proteins - metabolism</topic><topic>Tight junctions</topic><topic>Tight Junctions - metabolism</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Tumor necrosis factor-α</topic><topic>Zonula occludens-1 protein</topic><topic>Zonula Occludens-1 Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuki, Takuo</creatorcontrib><creatorcontrib>Tobiishi, Megumi</creatorcontrib><creatorcontrib>Kusaka-Kikushima, Ayumi</creatorcontrib><creatorcontrib>Ota, Yukiko</creatorcontrib><creatorcontrib>Tokura, Yoshiki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuki, Takuo</au><au>Tobiishi, Megumi</au><au>Kusaka-Kikushima, Ayumi</au><au>Ota, Yukiko</au><au>Tokura, Yoshiki</au><au>Koval, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-09-02</date><risdate>2016</risdate><volume>11</volume><issue>9</issue><spage>e0161759</spage><epage>e0161759</epage><pages>e0161759-e0161759</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. Western blot and immunohistochemical analyses revealed that the levels of zonula occludens 1 were decreased in the nonlesional sites of AD, and the levels of zonula occludens 1 and claudin-1 were decreased in the lesional sites relative to the levels in skin from healthy subjects. Next, we examined the effects of interleukin (IL)-4, tumor necrosis factor-α, IL-17, and IL-22 on the TJ barrier in a skin-equivalent model. Only IL-17 impaired the TJ barrier. Furthermore, we observed a defect in filaggrin monomer degradation in the IL-17-treated skin model. Thus, TJs are dysfunctional in AD, at least partly, due to the effect of IL-17, which may result in an aberrant SC barrier.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27588419</pmid><doi>10.1371/journal.pone.0161759</doi><tpages>e0161759</tpages><oa>free_for_read</oa></addata></record>
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subjects Aberration
Analysis
Antigens
Atopic dermatitis
Biology and Life Sciences
Care and treatment
Cell adhesion
Cells, Cultured
Claudin-1 - metabolism
Clostridium perfringens
Cytokines
Dermatitis
Dermatitis, Atopic - metabolism
Dermatitis, Atopic - pathology
Disease
Eczema
Epidermis
Equivalence
Filaggrin
Filaggrin Proteins
Health aspects
Helper cells
Homeostasis
Humans
Interleukin 17
Interleukin 22
Interleukin-17 - pharmacology
Interleukin-4 - pharmacology
Interleukins - pharmacology
Keratinocytes - drug effects
Keratinocytes - metabolism
Keratinocytes - pathology
Localization
Lymphocytes T
Medicine and Health Sciences
Membrane proteins
Mutation
Pathogenesis
Pathogens
Physical Sciences
Pneumoviridae
Proteins
Psoriasis
Research and Analysis Methods
Risk factors
Skin
Skin - drug effects
Skin - metabolism
Skin - pathology
Skin diseases
Stratum corneum
Tight Junction Proteins - metabolism
Tight junctions
Tight Junctions - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Tumor necrosis factor-α
Zonula occludens-1 protein
Zonula Occludens-1 Protein - metabolism
title Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17
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