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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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. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0161759</identifier><identifier>PMID: 27588419</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0161759-e0161759</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Yuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Yuki et al 2016 Yuki et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-6e46d7679e25cbe9e0eed1648cb86da9ad1707611f923cc07bf7236aa56719653</citedby><cites>FETCH-LOGICAL-c725t-6e46d7679e25cbe9e0eed1648cb86da9ad1707611f923cc07bf7236aa56719653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010286/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010286/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27588419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Koval, Michael</contributor><creatorcontrib>Yuki, Takuo</creatorcontrib><creatorcontrib>Tobiishi, Megumi</creatorcontrib><creatorcontrib>Kusaka-Kikushima, Ayumi</creatorcontrib><creatorcontrib>Ota, Yukiko</creatorcontrib><creatorcontrib>Tokura, Yoshiki</creatorcontrib><title>Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Aberration</subject><subject>Analysis</subject><subject>Antigens</subject><subject>Atopic dermatitis</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Cell adhesion</subject><subject>Cells, Cultured</subject><subject>Claudin-1 - metabolism</subject><subject>Clostridium perfringens</subject><subject>Cytokines</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - metabolism</subject><subject>Dermatitis, Atopic - pathology</subject><subject>Disease</subject><subject>Eczema</subject><subject>Epidermis</subject><subject>Equivalence</subject><subject>Filaggrin</subject><subject>Filaggrin Proteins</subject><subject>Health aspects</subject><subject>Helper cells</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Interleukin 17</subject><subject>Interleukin 22</subject><subject>Interleukin-17 - 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pharmacology</subject><subject>Tumor necrosis factor-α</subject><subject>Zonula occludens-1 protein</subject><subject>Zonula Occludens-1 Protein - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBEQkJw2MUf8UculValwKKiSrRwtRxnsuuSxFvbKfDvcbZp1UU9VD7EHj_zxnpnJsteYjTHVOAPF27wvW7nG9fDHGGOBSsfZfu4pGTGCaKP7-z3smchXCDEqOT8abZHBJOywOV-1i27jbYe6vzcrtYx_zr0JlrXh9z2-SK6jTX5R_CdjjbakJ_9SmHd1-Ot3p5mx5eDvdIt9DH_5mpo83MPOibB3zau82UfwbcwjCQWz7MnjW4DvJi-B9mPT8fnR19mJ6efl0eLk5kRhMUZh4LXgosSCDMVlIAAaswLaSrJa13qGgskOMZNSagxSFSNIJRrzbjAJWf0IHt9rbtpXVCTU0FhiTkltMQ4Ectronb6Qm287bT_q5y2ahtwfqW0j9a0oFBdNGUtmC4IKyRrKo0FyIrSqiqNYJC0Dqe_DVUHtUlWeN3uiO7e9HatVu5KMYQRkTwJvJsEvLscIETV2WCgbXUPbhjfTYSUvJTyAWjqA445G1Xf_Ifeb8RErVINle0bl55oRlG1KDihiBE2Gjq_h0qrhs6a1IGNTfGdhPc7CYmJ8Ceu9BCCWp59fzh7-nOXfXuHXYNu4zq4dtj27C5YXIPGuxA8NLf1wEiNA3TjhhoHSE0DlNJe3a3lbdLNxNB_1g4UXQ</recordid><startdate>20160902</startdate><enddate>20160902</enddate><creator>Yuki, Takuo</creator><creator>Tobiishi, Megumi</creator><creator>Kusaka-Kikushima, Ayumi</creator><creator>Ota, Yukiko</creator><creator>Tokura, Yoshiki</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160902</creationdate><title>Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17</title><author>Yuki, Takuo ; Tobiishi, Megumi ; Kusaka-Kikushima, Ayumi ; Ota, Yukiko ; Tokura, Yoshiki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-6e46d7679e25cbe9e0eed1648cb86da9ad1707611f923cc07bf7236aa56719653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aberration</topic><topic>Analysis</topic><topic>Antigens</topic><topic>Atopic dermatitis</topic><topic>Biology and Life Sciences</topic><topic>Care and treatment</topic><topic>Cell adhesion</topic><topic>Cells, Cultured</topic><topic>Claudin-1 - 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 & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & 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 & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & 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 & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & 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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