Paeonol promotes the phagocytic ability of macrophages through confining HMGB1 to the nucleus

Int Immunopharmacol. 2020 Dec;89(Pt B):107068. doi: 10.1016/j.intimp.2020.107068. Epub 2020 Oct 19.

Abstract

Phagocytosis is a basic immune response to the pathogens invading. Immunosuppression may occur in diseases like sepsis and cancer, and cause a low phagocytic ability of phagocytes. High mobility group protein B1 (HMGB1) is a DNA chaperone which is closely related to the phagocytosis. Nonetheless, its influence on phagocytosis is still controversial. We found that paeonol could inhibit the translocation of HMGB1 from the nucleus to the cytoplasm, it may have an impact on phagocytosis. In the present study, we performed in vivo and in vitro experiments to investigate the influence of paeonol on phagocytosis. Zymosan was used to test the phagocytic function of macrophages. Our results showed that paeonol promotes the phagocytosis of macrophages through confining HMGB1 to the nucleus. Through interacting with P53, the nuclear HMGB1 keep it in the nucleus and decrease the negative influence of P53 on the phosphorylation of Focal Adhesion Kinase (FAK). The increasing of phosphorylated FAK promotes the formation of pseudopod and enhances the phagocytic ability of macrophages.

Keywords: FAK; HMGB1; P53; Paeonol; Phagocytosis.

MeSH terms

  • Acetophenones / pharmacology*
  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism
  • Focal Adhesion Kinase 1 / metabolism
  • HMGB1 Protein / metabolism*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis / drug effects*
  • Phosphorylation
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • RAW 264.7 Cells
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Acetophenones
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • Lipopolysaccharides
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • paeonol
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse