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.
| Original language | English |
|---|---|
| Pages (from-to) | 880-886 |
| Number of pages | 7 |
| Journal | Experimental dermatology |
| Volume | 25 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2016 Nov 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Dermatology
Cite this
}
Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of L-plastin in atopic dermatitis. / 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, Kwanghoon.
In: Experimental dermatology, Vol. 25, No. 11, 01.11.2016, p. 880-886.Research output: Contribution to journal › Article
TY - JOUR
T1 - Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of L-plastin in atopic dermatitis
AU - Noh, Ji Yeon
AU - Shin, Jung U.
AU - Park, Chang Ook
AU - Lee, Nara
AU - Jin, Shan
AU - Kim, Seo Hyeong
AU - Kim, Ji Hye
AU - Min, Arim
AU - Shin, Myeong Heon
AU - Lee, Kwanghoon
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85032698581&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032698581&partnerID=8YFLogxK
U2 - 10.1111/exd.13111
DO - 10.1111/exd.13111
M3 - Article
C2 - 27304220
AN - SCOPUS:85032698581
VL - 25
SP - 880
EP - 886
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 11
ER -