A Novel Anti-inflammatory Phenotype Transformed by Repetitive Low-dose Lipopolysaccharide in Primary Peritoneal Tissue-resident Macrophages

Anticancer Res. 2020 Aug;40(8):4457-4464. doi: 10.21873/anticanres.14450.


Background/aim: Our previous studies suggested that oral administration of lipopolysaccharide (LPS) regulates the progression of various diseases via transformation of tissue-resident macrophages (MΦ). Recently, we characterized microglia transformed by repetitive low-dose LPS treatment (REPELL-microglia) in vitro, and this response was similar to that observed in response to oral administration of LPS in vivo. Here, we examined the characteristics of peritoneal tissue-resident MΦ (pMΦ) transformed by repetitive low-dose LPS treatment (REPELL-pMΦ).

Materials and methods: Primary pMΦ were treated with low-dose LPS (1 ng/ml) three times; subsequently, phagocytic activity and gene expression were evaluated.

Results: REPELL-pMΦ exhibited high phagocytic activity and elevated expression of Arg1, Gipr, Gdnf, and Fpr2. The gene expression profiles observed in REPELL-pMΦ were distinct from those of REPELL-microglia.

Conclusion: REPELL-pMΦ have the potential to promote clearance of xenobiotics and to suppress inflammation. The present study also demonstrates the diversity of tissue-resident MΦ transformation that reflect their tissue origin.

Keywords: Repetitive low-dose lipopolysaccharide; anti-inflammation; phagocytosis; tissue-resident macrophages.

MeSH terms

  • Administration, Oral
  • Animals
  • Arginase / genetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor / genetics*
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / adverse effects*
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / physiology*
  • Male
  • Mice
  • Organ Specificity
  • Phagocytosis / drug effects
  • Phenotype
  • Primary Cell Culture
  • Receptors, Formyl Peptide / genetics*
  • Receptors, Gastrointestinal Hormone / genetics*
  • Up-Regulation


  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Lipopolysaccharides
  • Receptors, Formyl Peptide
  • Receptors, Gastrointestinal Hormone
  • formyl peptide receptor 2, mouse
  • gastric inhibitory polypeptide receptor
  • Arg1 protein, mouse
  • Arginase