Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis
Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an...
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Veröffentlicht in: | Experimental dermatology 2016-11, Vol.25 (11), p.880-886 |
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description | Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP‐inducible protein l‐plastin and confirmed upregulation of l‐plastin and p‐l‐plastin in TSLP‐treated human eosinophilic leukaemic (EoL‐1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)‐3, IL‐4, IL‐5 or IL‐13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l‐plastin and an increase in migration of TSLP and cytokine‐treated eosinophils. In addition, phosphorylation of l‐plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP‐induced phosphorylation of l‐plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p‐l‐plastin as a potential drug target for eosinophil‐targeted allergy therapy. |
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Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP‐inducible protein l‐plastin and confirmed upregulation of l‐plastin and p‐l‐plastin in TSLP‐treated human eosinophilic leukaemic (EoL‐1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)‐3, IL‐4, IL‐5 or IL‐13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l‐plastin and an increase in migration of TSLP and cytokine‐treated eosinophils. In addition, phosphorylation of l‐plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP‐induced phosphorylation of l‐plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p‐l‐plastin as a potential drug target for eosinophil‐targeted allergy therapy.</description><identifier>ISSN: 0906-6705</identifier><identifier>EISSN: 1600-0625</identifier><identifier>DOI: 10.1111/exd.13111</identifier><identifier>PMID: 27304220</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>atopic dermatitis ; Case-Control Studies ; Cell Line, Tumor ; Cytokines - metabolism ; Dermatitis, Atopic - immunology ; Dermatitis, Atopic - metabolism ; eosinophil ; Eosinophils - metabolism ; Humans ; Membrane Glycoproteins - metabolism ; Microfilament Proteins - metabolism ; migration ; phospho-l-plastin ; Phosphorylation ; thymic stromal lymphopoietin</subject><ispartof>Experimental dermatology, 2016-11, Vol.25 (11), p.880-886</ispartof><rights>2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4621-a9b668117538e285d93dfeb1465ffb14db4c58ae24cc254c007f0ce2270cfdc63</citedby><cites>FETCH-LOGICAL-c4621-a9b668117538e285d93dfeb1465ffb14db4c58ae24cc254c007f0ce2270cfdc63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fexd.13111$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fexd.13111$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27304220$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noh, Ji Yeon</creatorcontrib><creatorcontrib>Shin, Jung U</creatorcontrib><creatorcontrib>Park, Chang Ook</creatorcontrib><creatorcontrib>Lee, Nara</creatorcontrib><creatorcontrib>Jin, Shan</creatorcontrib><creatorcontrib>Kim, Seo Hyeong</creatorcontrib><creatorcontrib>Kim, Ji Hye</creatorcontrib><creatorcontrib>Min, Arim</creatorcontrib><creatorcontrib>Shin, Myeong Heon</creatorcontrib><creatorcontrib>Lee, Kwang Hoon</creatorcontrib><title>Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis</title><title>Experimental dermatology</title><addtitle>Exp Dermatol</addtitle><description>Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP‐inducible protein l‐plastin and confirmed upregulation of l‐plastin and p‐l‐plastin in TSLP‐treated human eosinophilic leukaemic (EoL‐1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)‐3, IL‐4, IL‐5 or IL‐13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l‐plastin and an increase in migration of TSLP and cytokine‐treated eosinophils. In addition, phosphorylation of l‐plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP‐induced phosphorylation of l‐plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p‐l‐plastin as a potential drug target for eosinophil‐targeted allergy therapy.</description><subject>atopic dermatitis</subject><subject>Case-Control Studies</subject><subject>Cell Line, Tumor</subject><subject>Cytokines - metabolism</subject><subject>Dermatitis, Atopic - immunology</subject><subject>Dermatitis, Atopic - metabolism</subject><subject>eosinophil</subject><subject>Eosinophils - metabolism</subject><subject>Humans</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Microfilament Proteins - metabolism</subject><subject>migration</subject><subject>phospho-l-plastin</subject><subject>Phosphorylation</subject><subject>thymic stromal lymphopoietin</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1P3DAQhq2qqGxpD_0DVY7lEBjbsZ0cEV-txMeFCm6W15mwLs462FlK_n29DXCrVGusGY2e9z3MS8gXCgc0v0N8bg8oz9M7sqASoATJxHuygAZkKRWIXfIxpV8AVHElPpBdpjhUjMGCPN6spt7ZIo0x9MYXfuqHVRiCw9Gti4j3G29GTAWG5NZhWDlf9O4-mtGFdfHkTJHplH-c_LwLXeHLwZu01ecyYxiyf4uxz8Do0iey0xmf8PNL3yM_z05vjr-XF9fnP46PLkpbSUZL0yylrClVgtfIatE2vO1wSSspui63dllZURtklbVMVBZAdWCRMQW2a63ke-Tb7DvE8LjBNOreJYvemzWGTdK05oo1oqrof6AsX5FJ4Bndn1EbQ0oROz1E15s4aQp6G4bOYei_YWT264vtZtlj-0a-Xj8DhzPw23mc_u2kT-9OXi3LWeHSiM9vChMftNxmq2-vzrW4PJP13a3SDf8DSbOkvQ</recordid><startdate>201611</startdate><enddate>201611</enddate><creator>Noh, Ji Yeon</creator><creator>Shin, Jung U</creator><creator>Park, Chang Ook</creator><creator>Lee, Nara</creator><creator>Jin, Shan</creator><creator>Kim, Seo Hyeong</creator><creator>Kim, Ji Hye</creator><creator>Min, Arim</creator><creator>Shin, Myeong Heon</creator><creator>Lee, Kwang Hoon</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201611</creationdate><title>Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis</title><author>Noh, Ji Yeon ; Shin, Jung U ; Park, Chang Ook ; Lee, Nara ; Jin, Shan ; Kim, Seo Hyeong ; Kim, Ji Hye ; Min, Arim ; Shin, Myeong Heon ; Lee, Kwang Hoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4621-a9b668117538e285d93dfeb1465ffb14db4c58ae24cc254c007f0ce2270cfdc63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>atopic dermatitis</topic><topic>Case-Control Studies</topic><topic>Cell Line, Tumor</topic><topic>Cytokines - metabolism</topic><topic>Dermatitis, Atopic - immunology</topic><topic>Dermatitis, Atopic - metabolism</topic><topic>eosinophil</topic><topic>Eosinophils - metabolism</topic><topic>Humans</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Microfilament Proteins - metabolism</topic><topic>migration</topic><topic>phospho-l-plastin</topic><topic>Phosphorylation</topic><topic>thymic stromal lymphopoietin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noh, Ji Yeon</creatorcontrib><creatorcontrib>Shin, Jung U</creatorcontrib><creatorcontrib>Park, Chang Ook</creatorcontrib><creatorcontrib>Lee, Nara</creatorcontrib><creatorcontrib>Jin, Shan</creatorcontrib><creatorcontrib>Kim, Seo Hyeong</creatorcontrib><creatorcontrib>Kim, Ji Hye</creatorcontrib><creatorcontrib>Min, Arim</creatorcontrib><creatorcontrib>Shin, Myeong Heon</creatorcontrib><creatorcontrib>Lee, Kwang Hoon</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Experimental dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noh, Ji Yeon</au><au>Shin, Jung U</au><au>Park, Chang Ook</au><au>Lee, Nara</au><au>Jin, Shan</au><au>Kim, Seo Hyeong</au><au>Kim, Ji Hye</au><au>Min, Arim</au><au>Shin, Myeong Heon</au><au>Lee, Kwang Hoon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis</atitle><jtitle>Experimental dermatology</jtitle><addtitle>Exp Dermatol</addtitle><date>2016-11</date><risdate>2016</risdate><volume>25</volume><issue>11</issue><spage>880</spage><epage>886</epage><pages>880-886</pages><issn>0906-6705</issn><eissn>1600-0625</eissn><abstract>Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP‐inducible protein l‐plastin and confirmed upregulation of l‐plastin and p‐l‐plastin in TSLP‐treated human eosinophilic leukaemic (EoL‐1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)‐3, IL‐4, IL‐5 or IL‐13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l‐plastin and an increase in migration of TSLP and cytokine‐treated eosinophils. In addition, phosphorylation of l‐plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP‐induced phosphorylation of l‐plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p‐l‐plastin as a potential drug target for eosinophil‐targeted allergy therapy.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>27304220</pmid><doi>10.1111/exd.13111</doi><tpages>7</tpages></addata></record> |
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subjects | atopic dermatitis Case-Control Studies Cell Line, Tumor Cytokines - metabolism Dermatitis, Atopic - immunology Dermatitis, Atopic - metabolism eosinophil Eosinophils - metabolism Humans Membrane Glycoproteins - metabolism Microfilament Proteins - metabolism migration phospho-l-plastin Phosphorylation thymic stromal lymphopoietin |
title | Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l-plastin in atopic dermatitis |
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