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
Hauptverfasser: 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
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container_end_page 886
container_issue 11
container_start_page 880
container_title Experimental dermatology
container_volume 25
creator 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
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.
doi_str_mv 10.1111/exd.13111
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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 &amp; Sons A/S. 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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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