Open Access

Epigenetic regulation of COX‑2 expression by DNA hypomethylation via NF‑κB activation in ketamine‑induced ulcerative cystitis

  • Authors:
    • Shu‑Mien Chuang
    • Jian‑He Lu
    • Kun‑Ling Lin
    • Cheng‑Yu Long
    • Yung‑Chin Lee
    • Hui‑Pin Hsiao
    • Chia‑Chun Tsai
    • Wen‑Jeng Wu
    • Hui‑Jun Yang
    • Yung‑Shun Juan
  • View Affiliations

  • Published online on: June 21, 2019     https://doi.org/10.3892/ijmm.2019.4252
  • Pages: 797-812
  • Copyright: © Chuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the methylation of CpG sites in the cyclooxygenase (COX)‑2 promoter via nuclear factor (NF)‑κB transcriptional regulation and elucidated its effect on the COX‑2 transcriptional expression in a ketamine‑induced ulcerative cystitis (KIC) animal model. The results of the present study revealed that ketamine treatment induced NF‑κB p65 translocation to nuclei and activated COX‑2 expression and prostaglandin (PGE)2 production in bladder tissue, whereas COX‑2 inhibitor suppressed the inflammatory effect. Moreover, DNA hypomethylation of the COX‑2 promoter region located from ‑1,522 to ‑829 bp might contribute to transcriptional regulation of COX‑2 expression and induce a pro‑inflammatory response in KIC. Ketamine treatment increased the binding of NF‑κB and permissive histone H3 lysine‑4 (H3K4)m3, but caused a decrease in the repressive histone H3K27m3 and H3K36m3 on the COX‑2 promoter ranging from ‑1,522 to ‑1,331 bp as determined by a chromatin immunoprecipitation assay. Moreover, in the ketamine group, the level of Ten‑Eleven‑Translocation methylcytosine dioxygenase for demethylation as determined by reverse transcription‑quantitative PCR assay was increased in comparison with the control group, but that was not the case for the level of DNA methyltransferases for methylation. The present findings revealed that there was a hypomethylation pattern of the COX‑2 promoter in association with the level of COX‑2 transcription in KIC.

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September 2019
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Copy and paste a formatted citation
APA
Chuang, S., Lu, J., Lin, K., Long, C., Lee, Y., Hsiao, H. ... Juan, Y. (2019). Epigenetic regulation of COX‑2 expression by DNA hypomethylation via NF‑κB activation in ketamine‑induced ulcerative cystitis. International Journal of Molecular Medicine, 44, 797-812. https://doi.org/10.3892/ijmm.2019.4252
MLA
Chuang, S., Lu, J., Lin, K., Long, C., Lee, Y., Hsiao, H., Tsai, C., Wu, W., Yang, H., Juan, Y."Epigenetic regulation of COX‑2 expression by DNA hypomethylation via NF‑κB activation in ketamine‑induced ulcerative cystitis". International Journal of Molecular Medicine 44.3 (2019): 797-812.
Chicago
Chuang, S., Lu, J., Lin, K., Long, C., Lee, Y., Hsiao, H., Tsai, C., Wu, W., Yang, H., Juan, Y."Epigenetic regulation of COX‑2 expression by DNA hypomethylation via NF‑κB activation in ketamine‑induced ulcerative cystitis". International Journal of Molecular Medicine 44, no. 3 (2019): 797-812. https://doi.org/10.3892/ijmm.2019.4252