IL-33 down-regulates CLDN1 expression through the ERK/STAT3 pathway in keratinocytes

Woo In Ryu, Hana Lee, Hyun Cheol Bae, Jiehyun Jeon, Hwa Jung Ryu, Jaehyung Kim, Ji Hyun Kim, Ji Won Son, Jae Young Kim, Yasutomo Imai, Kiyofumi Yamanishi, Sang Hoon Jeong, Sang Wook Son

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)


Background: Tight junctions (TJs) have important roles in skin barrier function. The TJ protein claudin-1 (CLDN1) is decreased in atopic dermatitis (AD). However, little is known about the mechanism of CLDN1 down-expression. Objective: To elucidate the effect of IL-33 on CLDN1 expression in keratinocytes. Methods: Normal human epidermal keratinocytes (NHEKs) and human skin equivalent models (HSEMs) were cultured in vitro in the presence of IL-33. Production of CLDN1, signal transducer and activator of transcription 3 (STAT3) and Mitogen-activated protein kinases (MAPK) expression were measured by real-time PCR, western blot and immunofluorescence assay. MAPK inhibitors and small interfering RNA were used to confirm the signal pathway of STAT3 and CLDN1. Barrier function was measured by transepithelial electric resistance (TEER) and FITC-dextran flux assays. Electrophoretic Mobility Shift Assay was used to detect STAT3 transcriptional activity. Results: Levels of CLDN1 expression were reduced in the epidermis of AD-model mice overexpressing IL-33. IL-33 down-regulated the expression of CLDN1 mRNA and protein in NHEKs and HSEMs. IL-33 attenuated transepithelial electric resistance and induced FITC-dextran flux in NHEKs. The IL-33 suppressed CLDN1 expression was regulated by an extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3). STAT3 suppressed CLDN1 expression by direct binding to the promoters. Conclusion: IL-33 may down-regulate CLDN1 expression through the ERK/STAT3 pathway in keratinocytes.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalJournal of Dermatological Science
Issue number3
Publication statusPublished - 2018 Jun

Bibliographical note

Publisher Copyright:
© 2018 Japanese Society for Investigative Dermatology


  • Claudin 1
  • Extracellular signal-regulated kinase
  • IL-33
  • Keratinocytes
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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