Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory response in LPS-driven human macrophages

Junya Kaneko, Toshinori Okinaga, Wataru Ariyoshi, Hisako Hikiji, Seiko Fujii, Kenjiro Iwanaga, Kazuhiro Tominaga, Tatsuji Nishihara

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Histone deacetylase has attracted much attention as an epigenetic factor, and the modulation of histone and transcription factor acetylation status is important for regulating gene expression. Moreover, histone deacetylase inhibitors are involved in cellular growth and differentiation. In the present study, we examined the effects of Ky-2, a hybrid-compound HDAC inhibitor, on inflammatory reactions and the polarization of macrophages in vitro. Human monocyte-like THP-1 cells were polarized to macrophage-like cells using phorbol 12-myristate 13-acetate, and then polarized to M1 macrophages with LPS. Ky-2 inhibited HDAC2 expression and enhanced the acetylation of histone H3 in THP-1 cells. It also downregulated the expression of the IL-1β-encoding gene and the LPS-induced phosphorylation of p38 mitogen-activated protein kinases in THP-1 cells. Moreover, the expression of nod-like receptor protein 3 and cleaved caspase-1 p20 was downregulated in Ky-2-treated THP-1 cells. In contrast, this agent upregulated the expression of IL-1ra in LPS-treated THP-1 cells. These results indicate that Ky-2-treatment downregulates the expression of the inflammatory cytokine, IL-1β, in LPS-treated THP-1 cells, suggesting that Ky-2 might regulate M1 macrophage polarization through the suppression of inflammatory responses such as NLRP3 inflammasome activation.

Original languageEnglish
Pages (from-to)1622-1631
Number of pages10
JournalCell Biology International
Volume42
Issue number12
DOIs
Publication statusPublished - 2018 Dec

Keywords

  • HDAC inhibitor
  • MAPK
  • histone deacetylase
  • inflammasome
  • macrophage polarization

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory response in LPS-driven human macrophages'. Together they form a unique fingerprint.

Cite this