Upregulation of lysine‐specific demethylase 6B aggravates inflammatory pain through H3K27me3 demethylation‐dependent production of TNF‐α in the dorsal root ganglia and spinal dorsal horn in rats

Author:

Qiao Yiming1,Li Liren1,Bai Liying12,Gao Yan1,Yang Yin1,Wang Li1,Wang Xueli1,Liang Zongyi1,Xu Ji‐Tian13ORCID

Affiliation:

1. Department of Physiology and Neurobiology, School of Basic Medical Sciences Zhengzhou University Zhengzhou China

2. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital Zhengzhou University Zhengzhou China

3. Neuroscience Research Institute Zhengzhou University Zhengzhou China

Abstract

AbstractAimsLysine‐specific demethylase 6B (KDM6B) serves as a key mediator of gene transcription. It regulates expression of proinflammatory cytokines and chemokines in variety of diseases. Herein, the role and the underlying mechanisms of KDM6B in inflammatory pain were studied.MethodsThe inflammatory pain was conducted by intraplantar injection of complete Freund's adjuvant (CFA) in rats. Immunofluorescence, Western blotting, qRT‐PCR, and chromatin immunoprecipitation (ChIP)‐PCR were performed to investigate the underlying mechanisms.ResultsCFA injection led to upregulation of KDM6B and decrease in the level of H3K27me3 in the dorsal root ganglia (DRG) and spinal dorsal horn. The mechanical allodynia and thermal hyperalgesia following CFA were alleviated by the treatment of intrathecal injection of GSK‐J4, and by microinjection of AAV‐EGFP‐KDM6B shRNA in the sciatic nerve or in lumbar 5 dorsal horn. The increased production of tumor necrosis factor‐α (TNF‐α) following CFA in the DRGs and dorsal horn was inhibited by these treatments. ChIP‐PCR showed that CFA‐induced increased binding of nuclear factor κB with TNF‐α promoter was repressed by the treatment of microinjection of AAV‐EGFP‐KDM6B shRNA.ConclusionsThese results suggest that upregulated KDM6B via facilitating TNF‐α expression in the DRG and spinal dorsal horn aggravates inflammatory pain.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology

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