Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2)-type immune responses are dominant. Th2 cytokine, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) have been suggested to have an important role in AD. IL-33 is highly expressed in AD, but its role in AD has not yet been fully understood. To further identify the role of IL-33 in AD, we investigated the expression of TSLP induced by IL-33 in keratinocytes. This study revealed that IL-33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)-1, which is an inflammatory transcriptional factor, is induced by IL-33. IL-33-mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen-activated protein kinase (MAPK) inhibitors or small interfering RNA against Egr-1. Chromatin immunoprecipitation (ChIP) assay indicated the direct involvement of Egr-1 in IL-33-mediated TSLP induction. Taken together, these findings indicate that IL-33 may increase TSLP expression through an Egr-1-dependent mechanism via ERK1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL-33-ERK/JNK/p38/Egr-1/TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.
| Original language | English |
|---|---|
| Pages (from-to) | 857-863 |
| Number of pages | 7 |
| Journal | Experimental Dermatology |
| Volume | 24 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2015 Nov 1 |
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Keywords
- Atopic dermatitis
- Early growth response protein 1
- Interleukin-33
- Mitogen-activated protein kinase
- Thymic stromal lymphopoietin
ASJC Scopus subject areas
- Biochemistry
- Medicine(all)
- Molecular Biology
- Dermatology
Cite this
IL-33 induces Egr-1-dependent TSLP expression via the MAPK pathways in human keratinocytes. / Ryu, Woo In; Lee, Hana; Kim, Jin Hee; Bae, Hyun Cheol; Ryu, Hwa Jung; Son, Sang Wook.
In: Experimental Dermatology, Vol. 24, No. 11, 01.11.2015, p. 857-863.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IL-33 induces Egr-1-dependent TSLP expression via the MAPK pathways in human keratinocytes
AU - Ryu, Woo In
AU - Lee, Hana
AU - Kim, Jin Hee
AU - Bae, Hyun Cheol
AU - Ryu, Hwa Jung
AU - Son, Sang Wook
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2)-type immune responses are dominant. Th2 cytokine, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) have been suggested to have an important role in AD. IL-33 is highly expressed in AD, but its role in AD has not yet been fully understood. To further identify the role of IL-33 in AD, we investigated the expression of TSLP induced by IL-33 in keratinocytes. This study revealed that IL-33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)-1, which is an inflammatory transcriptional factor, is induced by IL-33. IL-33-mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen-activated protein kinase (MAPK) inhibitors or small interfering RNA against Egr-1. Chromatin immunoprecipitation (ChIP) assay indicated the direct involvement of Egr-1 in IL-33-mediated TSLP induction. Taken together, these findings indicate that IL-33 may increase TSLP expression through an Egr-1-dependent mechanism via ERK1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL-33-ERK/JNK/p38/Egr-1/TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.
AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2)-type immune responses are dominant. Th2 cytokine, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) have been suggested to have an important role in AD. IL-33 is highly expressed in AD, but its role in AD has not yet been fully understood. To further identify the role of IL-33 in AD, we investigated the expression of TSLP induced by IL-33 in keratinocytes. This study revealed that IL-33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)-1, which is an inflammatory transcriptional factor, is induced by IL-33. IL-33-mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen-activated protein kinase (MAPK) inhibitors or small interfering RNA against Egr-1. Chromatin immunoprecipitation (ChIP) assay indicated the direct involvement of Egr-1 in IL-33-mediated TSLP induction. Taken together, these findings indicate that IL-33 may increase TSLP expression through an Egr-1-dependent mechanism via ERK1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL-33-ERK/JNK/p38/Egr-1/TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.
KW - Atopic dermatitis
KW - Early growth response protein 1
KW - Interleukin-33
KW - Mitogen-activated protein kinase
KW - Thymic stromal lymphopoietin
UR - http://www.scopus.com/inward/record.url?scp=84983161305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983161305&partnerID=8YFLogxK
U2 - 10.1111/exd.12788
DO - 10.1111/exd.12788
M3 - Article
C2 - 26120956
AN - SCOPUS:84983161305
VL - 24
SP - 857
EP - 863
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 11
ER -