Glycolaldehyde-derived advanced glycation end products suppress STING/TBK1/IRF3 signaling via CD36

Takashi Nishinaka, Omer Faruk Hatipoglu, Hidenori Wake, Masahiro Watanabe, Takao Toyomura, Shuji Mori, Masahiro Nishibori, Hideo Takahashi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Aims: We have previously reported that advanced glycation end products derived from incubation of albumin with glycolaldehyde (glycol-AGE), lead to suppression of the toll-like receptor 4 (TLR4) signaling response to lipopolysaccharide. Glycol-AGE-induced suppression of TLR4 signaling is involved in the downregulation of CD14, which is an adaptor protein necessary for transferring lipopolysaccharide to TLR4. Therefore, glycol-AGEs impair the innate immune response through suppression of the upstream process in TLR4 signaling. However, the effect of glycol-AGEs on intracellular signaling related to the innate immune response remains unclear. This study aimed to examined the effect of glycol-AGEs on stimulator of interferon gene (STING) signaling in macrophages. Main methods: In differentiated THP-1 cells, which are a human monocytic leukemia cell line, cyclic GMP-AMP (cGAMP) transfection was used to activate STING signaling. The phosphorylation levels of TANK-binding kinase 1 (TBK1)/interferon regulatory transcription factor 3 (IRF3) were evaluated by western blot analysis. Downstream cytokine levels were evaluated by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays. Key findings: Glycol-AGEs suppressed cGAMP-induced phosphorylation of TBK1 and IRF3, as well as the production of cytokines regulated by IRF3. There was no effect of glycol-AGEs on the efficacy of cGAMP transfection. Treatment of a neutralizing antibody against CD36 prevented cGAMP-induced phosphorylation of TBK1 and IRF3, and also upregulation of interferon-β and C-X-C motif chemokine ligand 10 in glycol-AGE-treated cells. Significance: Glycol-AGEs negatively regulate cGAMP-induced activation of STING/TBK1/IRF3 signaling via CD36. Our findings suggest that glycol-AGEs lead to impairment of the innate immune response by suppressing intracellular signaling.

Original languageEnglish
Article number121116
JournalLife Sciences
Publication statusPublished - Dec 1 2022
Externally publishedYes


  • Advanced glycation end products
  • Diabetes
  • Macrophage
  • Scavenger receptor class B member 3 (CD36)
  • STING signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


Dive into the research topics of 'Glycolaldehyde-derived advanced glycation end products suppress STING/TBK1/IRF3 signaling via CD36'. Together they form a unique fingerprint.

Cite this