IL-33 induces Egr-1-dependent TSLP expression via the MAPK pathways in human keratinocytes

Woo In Ryu, Hana Lee, Jin Hee Kim, Hyun Cheol Bae, Hwa Jung Ryu, Sang Wook Son

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


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 languageEnglish
Pages (from-to)857-863
Number of pages7
JournalExperimental Dermatology
Issue number11
Publication statusPublished - 2015 Nov 1

Bibliographical note

Publisher Copyright:
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • Atopic dermatitis
  • Early growth response protein 1
  • Interleukin-33
  • Mitogen-activated protein kinase
  • Thymic stromal lymphopoietin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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