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Targeted Epigenetic Silencing of Jumonji Domain-Containing Protein 3 Alleviates Nuclear Factor-Kappa B-Mediated

Ghada Nour Eldeen1, Mona F Sokkar1, Randa S Lotfy1

  • 1Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Centre, Egypt.

Archives of Medical Research
|May 23, 2026
PubMed
Abstract

Insights

In Familial Mediterranean Fever (FMF), inhibiting JMJD3 with GSK-J4 suppressed inflammasome activation and reduced key inflammatory markers. This highlights JMJD3 as a potential therapeutic target for autoinflammatory diseases.

Area of Science:

  • Inflammation research
  • Molecular biology
  • Genetics

Background:

  • Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease linked to MEFV gene variants and inflammasome dysregulation.
  • Nuclear factor-kappa B (NF-κB) is a key mediator of chronic inflammation in autoinflammatory conditions.
  • Jumonji domain-containing protein 3 (JMJD3) is an epigenetic regulator implicated in inflammation, with its inhibitor GSK-J4 showing potential therapeutic benefits.

Purpose of the Study:

  • To investigate the role of JMJD3 and NF-κB-JMJD3 signaling in inflammation.
  • To evaluate the efficacy of GSK-J4 in inhibiting inflammasome activation in FMF patient cells.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from FMF patients were cultured and stimulated.
  • Cells were treated with GSK-J4 or subjected to JMJD3 knockdown via siRNA.
  • Inflammatory markers and gene expression were analyzed using Western blotting, ELISA, and qRT-PCR.

Main Results:

  • GSK-J4 treatment significantly downregulated NF-κB, NLRP3, and inflammatory cytokine gene expression.
  • Western blotting confirmed reduced NF-κB levels post-GSK-J4 treatment.
  • JMJD3 knockdown also decreased inflammatory markers, confirming its pro-inflammatory role.

Conclusions:

  • Selective inhibition or silencing of JMJD3 effectively suppresses inflammasome activation in FMF.
  • JMJD3 represents a promising therapeutic target for managing inflammation in FMF and other autoinflammatory diseases.
Keywords:
Familial Mediterranean feverGSK-J4InflammasomeJMJD3siRNA

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