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Histone methylation and demethylation are implicated in the transient and sustained activation of the interleukin-1β gene in murine macrophages

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Abstract

Macrophages play a crucial role in the development of atherosclerosis. To explore the mechanism by which macrophages attain a proinflammatory phenotype for a sustained period, we stimulated macrophages with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) and measured the interleukin-1β (IL-1β) expression. The IL-1β expression increased transiently, and its expression lasted for, at least, 1 week after the cessation of LPS and IFN-γ stimulation. At the promoter region of the IL-1β gene, the demethylation of histone H3 lysine 27 (H3K27) was significantly induced for 1 week after transient stimulation with LPS and IFN-γ. The expression of H3K27 demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) and jumonji domain-containing 3 (JMJD3) increased significantly for 1 week after transient stimulation with LPS and IFN-γ. When the UTX expression was inhibited by using small interfering RNA (siRNA) for UTX, the IL-1β expression was significantly suppressed in both transient and sustained phases, whereas siRNA for JMJD3 significantly inhibited only the sustained phase of the IL-1β expression. These results suggested that H3K27 demethylation was implicated in the transient and sustained increase in the IL-1β expression after LPS and IFN-γ stimulation.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hiroyuki Imuta, Daishi Fujita & Arihiro Kiyosue

  2. Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan

    Shigeyoshi Oba

  3. Department of Urology, Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan

    Hiroaki Nishimatsu

  4. Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8512, Japan

    Kazuo Yudo & Etsu Suzuki

Authors
  1. Hiroyuki Imuta
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  2. Daishi Fujita
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  3. Shigeyoshi Oba
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  4. Arihiro Kiyosue
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  5. Hiroaki Nishimatsu
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  6. Kazuo Yudo
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  7. Etsu Suzuki
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Correspondence to Etsu Suzuki.

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Imuta, H., Fujita, D., Oba, S. et al. Histone methylation and demethylation are implicated in the transient and sustained activation of the interleukin-1β gene in murine macrophages. Heart Vessels 35, 1746–1754 (2020). https://doi.org/10.1007/s00380-020-01670-5

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  • DOI: https://doi.org/10.1007/s00380-020-01670-5

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