Identification of ribosomal protein L9 as a novel regulator of proinflammatory damage-associated molecular pattern molecules

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We previously reported that advanced glycation endproducts (AGEs) increase the proinflammatory activity of high mobility group box-1 (HMGB1), a representative damage-associated molecular pattern molecule (DAMP), through their direct interaction. This suggested that AGEs activate other DAMPs and led us to search for novel DAMPs capable of interacting with AGEs. Methods and results: The chromatographic analysis using AGE-immobilized gel revealed the ribosomal protein family to be a factor with binding activity to AGEs. Ribosomal protein L9 (RPL9), a member of the ribosomal protein family, was found in the centrifugal supernatant of ruptured cells and in the serum of lipopolysaccharide (LPS)-stimulated sepsis model mice, exhibiting similar characteristic properties to HMGB1. Although HMGB1 potentiated LPS-stimulated TNF-α expression in macrophage-like RAW264.7 cells, RPL9 hardly exhibited this activity. Of note, RPL9 significantly suppressed the potentiated mRNA expression and protein production of TNF-α by HMGB1 plus LPS stimulation, suggesting its regulatory roles in DAMP-induced proinflammatory activity. Based on the differential scanning fluorimetric analysis, the direct interaction between RPL9 and HMGB1 may play a role in the suppressive effects of RPL9. Conclusions: This study suggested that RPL9 is a novel type of DAMP with a regulatory role in the proinflammatory response and provided insight into the pathophysiology of inflammatory diseases.

Original languageEnglish
Pages (from-to)2831-2838
Number of pages8
JournalMolecular Biology Reports
Volume49
Issue number4
DOIs
Publication statusPublished - Apr 2022
Externally publishedYes

Keywords

  • Damage-associated molecular pattern molecules
  • High mobility group box-1
  • Lipopolysaccharide
  • Ribosomal protein L9

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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