Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa

J Immunol. 2000 Nov 1;165(9):5332-7. doi: 10.4049/jimmunol.165.9.5332.

Abstract

Helicobacter pylori (HP)-associated gastritis is characterized by an increased number of acute and chronic inflammatory cells secreting cytokines that contribute to maintain and expand the local inflammation. Locally induced IL-8 is believed to play a major role in the HP-associated acute inflammatory response. Factors/mechanisms that regulate IL-8 induction are, however, not fully understood. In the present study we investigated whether HP infection is associated with an increased production of IL-17, a T cell-derived cytokine capable of modulating IL-8 gene expression. We showed that both IL-17 RNA transcripts and protein were expressed at a higher level in the whole gastric mucosal and lamina propria mononuclear cell samples from HP-infected patients than in those from uninfected subjects. HP: eradication was associated with a marked down-regulation of IL-17 expression. The addition of a neutralizing anti-IL-17 Ab to the gastric lamina propria mononuclear cell cultures resulted in a significant inhibition of IL-8 secretion, indicating that IL-17 contributes to enhance IL-8 in the HP-colonized gastric mucosa. Consistently, stimulation of MKN 28 cells, a gastric epithelial cell line, with IL-17 increased IL-8 secretion. Finally, conditioned medium from the IL-17-stimulated MKN 28 cell cultures promoted the in vitro polymorphonuclear leukocyte migration. This effect was inhibitable by a neutralizing IL-8 but not IL-17 Ab. Together, these data indicate that biologically active IL-17 production is increased during HP: infection, suggesting the possibility that this cytokine may play an important role in the inflammatory response to the HP colonization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / biosynthesis
  • Adjuvants, Immunologic / physiology
  • Adult
  • Aged
  • Cell Line
  • Cell-Free System / immunology
  • Cells, Cultured
  • Chemotaxis, Leukocyte / immunology
  • Female
  • Gastric Mucosa / immunology*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / immunology*
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / physiology
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Up-Regulation / immunology*

Substances

  • Adjuvants, Immunologic
  • Interleukin-17
  • Interleukin-8