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

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-a-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.

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    • Authors

    Choi YS, Park JA, Kim J, Rho SS, Park H, Kim YM, Kwon YG

    Institution

    Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.

    Source

    Biochemical and biophysical research communications 421:2 2012 May 4 pg 305-11

    MeSH

    Cell Adhesion
    Cell Nucleus
    Cells, Cultured
    Endothelial Cells
    Gene Knockdown Techniques
    Human Umbilical Vein Endothelial Cells
    Humans
    Inflammation
    Intercellular Adhesion Molecule-1
    Interleukins
    Monocytes
    Promoter Regions, Genetic
    Transcription Factor RelA
    Transcriptional Activation
    Tumor Necrosis Factor-alpha
    Vascular Cell Adhesion Molecule-1

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22708120