Nuclear IL-33 is a transcriptional regulator of NF-κB p65 and induces endothelial cell activation

Yeon Sook Choi, Jeong Ae Park, Jihye Kim, Seung Sik Rho, Hyojin Park, Young Myeong Kim, Young-Guen Kwon

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-κB complex and is involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-α-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-κB pathway; NF-κB p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-κB p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-κB p65.

Original languageEnglish
Pages (from-to)305-311
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume421
Issue number2
DOIs
Publication statusPublished - 2012 May 4

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Endothelial cells
Endothelial Cells
Chemical activation
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Chromatin
Interleukin-33
Chromatin Immunoprecipitation
RNA-Directed DNA Polymerase
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-1
Genetic Promoter Regions
Tumor Necrosis Factor-alpha
Western Blotting
Cytokines

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Choi, Yeon Sook ; Park, Jeong Ae ; Kim, Jihye ; Rho, Seung Sik ; Park, Hyojin ; Kim, Young Myeong ; Kwon, Young-Guen. / Nuclear IL-33 is a transcriptional regulator of NF-κB p65 and induces endothelial cell activation. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 421, No. 2. pp. 305-311.
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Nuclear IL-33 is a transcriptional regulator of NF-κB p65 and induces endothelial cell activation. / Choi, Yeon Sook; Park, Jeong Ae; Kim, Jihye; Rho, Seung Sik; Park, Hyojin; Kim, Young Myeong; Kwon, Young-Guen.

In: Biochemical and Biophysical Research Communications, Vol. 421, No. 2, 04.05.2012, p. 305-311.

Research output: Contribution to journalArticle

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