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 journalArticle

8 Citations (Scopus)

Abstract

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
JournalJournal of Dermatological Science
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Claudin-1
STAT3 Transcription Factor
Extracellular Signal-Regulated MAP Kinases
Keratinocytes
Down-Regulation
Assays
Skin
Atopic Dermatitis
Mitogen-Activated Protein Kinases
Electric Impedance
Zonula Occludens-1 Protein
Claudins
Interleukin-33
Fluxes
Tight Junction Proteins
Electrophoretic mobility
Tight Junctions
Electrophoretic Mobility Shift Assay
Protein Kinase Inhibitors
Epidermis

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

IL-33 down-regulates CLDN1 expression through the ERK/STAT3 pathway in keratinocytes. / Ryu, Woo In; Lee, Hana; Bae, Hyun Cheol; Jeon, Jiehyun; Ryu, Hwa Jung; Kim, Jaehyung; Kim, Ji Hyun; Son, Ji Won; Kim, Jae Young; Imai, Yasutomo; Yamanishi, Kiyofumi; Jeong, Sang Hoon; Son, Sang Wook.

In: Journal of Dermatological Science, 01.01.2018.

Research output: Contribution to journalArticle

Ryu, Woo In ; Lee, Hana ; Bae, Hyun Cheol ; Jeon, Jiehyun ; Ryu, Hwa Jung ; Kim, Jaehyung ; Kim, Ji Hyun ; Son, Ji Won ; Kim, Jae Young ; Imai, Yasutomo ; Yamanishi, Kiyofumi ; Jeong, Sang Hoon ; Son, Sang Wook. / IL-33 down-regulates CLDN1 expression through the ERK/STAT3 pathway in keratinocytes. In: Journal of Dermatological Science. 2018.
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title = "IL-33 down-regulates CLDN1 expression through the ERK/STAT3 pathway in keratinocytes",
abstract = "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.",
keywords = "Claudin 1, Extracellular signal-regulated kinase, IL-33, Keratinocytes, Signal transducer and activator of transcription 3",
author = "Ryu, {Woo In} and Hana Lee and Bae, {Hyun Cheol} and Jiehyun Jeon and Ryu, {Hwa Jung} and Jaehyung Kim and Kim, {Ji Hyun} and Son, {Ji Won} and Kim, {Jae Young} and Yasutomo Imai and Kiyofumi Yamanishi and Jeong, {Sang Hoon} and Son, {Sang Wook}",
year = "2018",
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language = "English",
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T1 - IL-33 down-regulates CLDN1 expression through the ERK/STAT3 pathway in keratinocytes

AU - Ryu, Woo In

AU - Lee, Hana

AU - Bae, Hyun Cheol

AU - Jeon, Jiehyun

AU - Ryu, Hwa Jung

AU - Kim, Jaehyung

AU - Kim, Ji Hyun

AU - Son, Ji Won

AU - Kim, Jae Young

AU - Imai, Yasutomo

AU - Yamanishi, Kiyofumi

AU - Jeong, Sang Hoon

AU - Son, Sang Wook

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Claudin 1

KW - Extracellular signal-regulated kinase

KW - IL-33

KW - Keratinocytes

KW - Signal transducer and activator of transcription 3

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DO - 10.1016/j.jdermsci.2018.02.017

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