Differential contribution of possible pattern-recognition receptors to advanced glycation end product–induced cellular responses in macrophage-like RAW264.7 cells

Masahiro Watanabe, Takao Toyomura, Hidenori Wake, Keyue Liu, Kiyoshi Teshigawara, Hideo Takahashi, Masahiro Nishibori, Shuji Mori

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Advanced glycation end products (AGEs) are considered to be related to the pathogenesis of some inflammatory diseases. AGEs were reported to stimulate the receptor for AGEs (RAGE), which causes inflammatory reactions. However, recently, toll-like receptors (TLRs), in addition to RAGE, have been reported to be related to AGE-mediated cellular responses, and it remains unclear which receptor is responsible for AGE recognition. To reveal the role of pattern-recognition receptors, including TLRs and/or RAGE, in AGE-mediated cellular responses, we generated macrophage-like RAW264.7 knockout (KO) cells lacking these receptors by genome editing using the CRISPR/Cas9 system and assessed AGE-stimulated changes in these cells. Comparison of the established clones suggested that RAGE partially affects the expression of TLRs. In the KO clone lacking TLR4 and TLR2, AGE-stimulated tumor necrosis factor alpha (TNF-α) expression and phosphorylation of IκBα, p38, and extracellular signal-regulated kinase (ERK) were significantly attenuated, suggesting that AGE-mediated responses are largely dependent on TLRs. On the other hand, on comparison of the AGE-stimulated responses between the KO clone lacking TLR4 and TLR2, and the clone lacking TLR4, TLR2, and RAGE, RAGE played little role in AGE-stimulated TNF-α transcription and ERK phosphorylation. Taken together, this study suggested that AGE-stimulated inflammatory responses occur mainly through TLRs rather than RAGE.

Original languageEnglish
Pages (from-to)265-272
Number of pages8
JournalBiotechnology and Applied Biochemistry
Volume67
Issue number2
DOIs
Publication statusPublished - Mar 1 2020

Keywords

  • advanced glycation end products
  • genome editing
  • knockout
  • receptor for advanced glycation end products
  • toll-like receptor

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Drug Discovery
  • Process Chemistry and Technology

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