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The interaction of O-GlcNAc-modified NLRX1 and IKK-α modulates IL-1β expression in M1 macrophages

Liqiong Chen1, Yueliang Li1,2, Shuxian Zeng1

  • 1Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.

In Vitro Cellular & Developmental Biology. Animal
|May 5, 2022
PubMed

Insights

NLRX1 protein modification by O-linked N-acetylglucosamine (O-GlcNAc) regulates inflammation. O-GlcNAcylation enhances NLRX1 ubiquitination and interaction with IKK-α, reducing inflammatory cytokine expression in macrophages.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • NOD-like receptor (NLR)X1 (NLRX1) negatively regulates inflammation by inhibiting nuclear factor-κB (NF-κB) signaling.
  • The post-translational modifications and specific regulatory roles of NLRX1 in macrophage inflammatory responses remain largely uncharacterized.

Purpose of the Study:

  • To investigate the post-translational modification of NLRX1.
  • To elucidate the role of NLRX1 O-GlcNAcylation in regulating inflammatory responses in macrophages.

Main Methods:

  • Co-immunoprecipitation and confocal microscopy to validate NLRX1 and O-GlcNAc transferase (OGT) interaction.
  • Ubiquitination assays and cycloheximide (CHX) chase experiments to assess NLRX1 stability.
  • Treatment with OGT inhibitor OSMI-1 to modulate O-GlcNAcylation levels.

Main Results:

  • NLRX1 was found to be modified with O-linked N-acetylglucosamine (O-GlcNAc).
  • Elevated O-GlcNAcylation promoted NLRX1 ubiquitination, decreased its stability, and enhanced its interaction with inhibitor of nuclear factor kappaB kinase-α (IKK-α).
  • These modifications led to reduced expression of the inflammatory cytokine IL-1β in M1 macrophages.

Conclusions:

  • The interaction between NLRX1 and O-GlcNAcylation serves as a critical regulatory mechanism.
  • This interplay modulates inflammatory processes within macrophages, impacting NF-κB signaling and cytokine production.
Keywords:
IKK-αInflammationNF-κBNLRX1O-GlcNAcylation

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