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Berberine demonstrates anti-inflammatory properties in Helicobacter pylori-infected mice with chronic gastritis by attenuating the Th17 response triggered by the B cell-activating factor

J Cell Biochem. 2018 Jul;119(7):5373-5381. doi: 10.1002/jcb.26681. Epub 2018 Mar 14.

Abstract

Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection is not fully understood. We investigated the anti-inflammatory properties and potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF-β, and IL-1β and upregulate anti-inflammatory gene IL-10 expression in the mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and accumulation of IL-17 in the mucosa and CD4+ T cells activated by anti-CD3 and anti-CD28, and it decreased the frequency of IL-17-producing CD4+ T cells. B cell-activating factor (BAFF) production was inhibited by BBR and by cultured dendritic and CD4+ T cells. Furthermore, we demonstrated that BAFF can trigger the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF-β, and IL-1β, which are strongly associated with the anti-inflammatory role of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by attenuating the BAFF-triggered Th17 response.

Keywords: BAFF; H. pylori; Th17; berberine; chronic gastritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism*
  • Berberine / pharmacology*
  • Cells, Cultured
  • Chronic Disease
  • Cytokines / metabolism
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / immunology
  • Gastric Mucosa / microbiology
  • Gastritis / drug therapy*
  • Gastritis / immunology
  • Gastritis / microbiology
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Interleukin-17 / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Th17 Cells / microbiology

Substances

  • Anti-Inflammatory Agents
  • B-Cell Activating Factor
  • Cytokines
  • Interleukin-17
  • Tnfsf13b protein, mouse
  • Berberine