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IL ‐33 induces Egr‐1‐dependent TSLP expression via the MAPK pathways in human keratinocytes
Author(s) -
Ryu WooIn,
Lee Hana,
Kim Jin Hee,
Bae Hyun Cheol,
Ryu Hwa Jung,
Son Sang Wook
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12788
Subject(s) - thymic stromal lymphopoietin , mapk/erk pathway , p38 mitogen activated protein kinases , chromatin immunoprecipitation , immunology , cytokine , immune system , allergic inflammation , protein kinase a , interleukin , inflammation , chemistry , microbiology and biotechnology , kinase , biology , gene expression , promoter , gene , biochemistry
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 (Ch IP ) 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 ERK 1/2, 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.