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TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages through JNK signaling pathway

Yanying An1, Yuqi Ni1, Zhihao Xu2

  • 1The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China.

Cellular Signalling
|December 29, 2019
PubMed

Insights

Tumor necrosis factor superfamily member 19 (TRIM59) expression in macrophages is regulated by Sp1 and Nrf1 transcription factors. Lipopolysaccharide (LPS) stimulation decreases TRIM59, impacting inflammatory diseases like atherosclerosis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Activated macrophages are key players in inflammatory diseases such as septic shock and atherosclerosis.
  • TRIM59 is implicated in various pathological processes including inflammation, cytotoxicity, and tumorigenesis.
  • The precise molecular mechanisms governing TRIM59 expression in activated macrophages remain incompletely understood.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling TRIM59 expression in lipopolysaccharide (LPS)-activated macrophages.
  • To investigate the roles of Sp1 and Nrf1 transcription factors in TRIM59 gene regulation.
  • To explore the potential of TRIM59 as a therapeutic target in inflammatory conditions.

Main Methods:

  • Analysis of TRIM59 expression in LPS-stimulated macrophages in vivo and in vitro.
  • Luciferase reporter assays to assess TRIM59 promoter activity.
  • Chromatin immunoprecipitation assays to determine Sp1 and Nrf1 binding to the TRIM59 promoter.
  • Assessment of the effect of JNK pathway inhibition on TRIM59 expression.
  • Evaluation of TRIM59 levels during atherosclerosis progression.

Main Results:

  • TRIM59 expression and promoter activity are significantly suppressed by LPS in macrophages.
  • Sp1 and Nrf1 directly bind to the proximal promoter of the TRIM59 gene.
  • LPS treatment decreases Sp1 but increases Nrf1 expression, nuclear translocation, and promoter binding.
  • Inhibition of the JNK signaling pathway reverses LPS-induced TRIM59 downregulation.
  • TRIM59 levels are notably reduced during the progression of atherosclerosis.

Conclusions:

  • TRIM59 expression in LPS-activated macrophages is precisely regulated by the opposing actions of Sp1 and Nrf1.
  • This regulation is potentially mediated through the JNK signaling pathway.
  • TRIM59 represents a promising therapeutic target for managing inflammatory diseases, particularly atherosclerosis.
Keywords:
AtherosclerosisMacrophageNrf1Sp1TRIM59

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