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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Published in | Experimental dermatology Vol. 25; no. 11; pp. 880 - 886 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Denmark
Blackwell Publishing Ltd
01.11.2016
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | National Research Foundation of Korea (NRF) Ministry of Health & Welfare, Republic of Korea - No. HI14C1324 Data S1 Supplementary Methods and Materials Figure S1 Proteomic analysis of TSLP-treated and untreated EoL-1 cells by 2D-DIGE analysis coupled with MALDI-TOF MS. Representative 2-DE images, comparative analysis of a differentially expressed L-plastin protein spot (a) and MS spectrum (b) Figure S2 Expression of p-L-plastin and L-plastin in TSLP treated EoL-1 cells. Treatment with TSLP increased phosphorylation of L-plastin in EoL-1 cells in dose-dependent (10-100 ng/ml, 24 h) and time-dependent (1-120 min, 50 ng/ml) manner. Expression of L-plastin did not differ between TSLP-treated and untreated EoL-1 cells Figure S3 Analysis of Western blot results in Figure 4a. Relative densities (%) were quantified by densitometric scanning. The values are the mean ± SD of two experiments. Data were analyzed by one-way analysis of variance, and significant differences were determined by the Tukey-Kramer test Table S1 Characteristics of the study subjects istex:18F18D9639D2BF74454AB08EE5A4DDF7019A8BDC Ministry of Education, Science and Technology - No. 2011-0016636 Korea Health Industry Development Institute (KHIDI) ark:/67375/WNG-5MF68XW7-9 ArticleID:EXD13111 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0906-6705 1600-0625 |
DOI: | 10.1111/exd.13111 |