BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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MicroRNA-22 negatively regulates LPS-induced inflammatory responses by targeting HDAC6 in macrophages

  • Youn, Gi Soo (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University) ;
  • Park, Jong Kook (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University) ;
  • Lee, Chae Yeon (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University) ;
  • Jang, Jae Hee (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University) ;
  • Yun, Sang Ho (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University) ;
  • Kwon, Hyeok Yil (Department of Physiology, College of Medicine, Hallym University) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University) ;
  • Park, Jinseu (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
  • Received : 2019.08.14
  • Accepted : 2019.10.01
  • Published : 2020.04.30
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Abstract

Dysregulation of histone deacetylase 6 (HDAC6) can lead to the pathologic states and result in the development of various diseases including cancers and inflammatory diseases. The objective of this study was to elucidate the regulatory role of microRNA-22 (miR-22) in HDAC6-mediated expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. LPS stimulation induced HDAC6 expression, but suppressed miR-22 expression in macrophages, suggesting possible correlation between HDAC6 and miR-22. Luciferase reporter assays revealed that 3'UTR of HDAC6 was a bona fide target site of miR-22. Transfection of miR-22 mimic significantly inhibited LPS-induced HDAC6 expression, while miR-22 inhibitor further increased LPS-induced HDAC6 expression. LPS-induced activation of NF-κB and AP-1 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. LPS-induced expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. Taken together, these data provide evidence that miR-22 can downregulate LPS-induced expression of pro-inflammatory cytokines via suppression of NF-κB and AP-1 axis by targeting HDAC6 in macrophages.

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References

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