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

72 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

Bibliographical note

Funding Information:
This study was supported by Grants from the Korea Health 21 R&D Project, Ministry of Health Welfare & Family Affairs, Republic of Korea (A085136), the National Research Foundation of Korea (NRF) funded by the Korean government (MEST, 2011-0020403 ), and the Biomedical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST, 2011-0019267 ).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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