Protein kinase C activation by Helicobacter pylori in human gastric epithelial cells limits interleukin-8 production through suppression of extracellular signal-regulated kinase

J Pharmacol Sci. 2004 Mar;94(3):233-9. doi: 10.1254/jphs.94.233.

Abstract

Helicobacter pylori (H. pylori) infection of gastric epithelial cells has been shown to induce interleukin (IL)-8 production, but the signal transduction mechanism leading to IL-8 production has not been clearly defined. Here, we investigate the role of protein kinase C (PKC) in the mechanism of induction of IL-8 release by H. pylori in human gastric epithelial cells. In MKN45 cells, H. pylori-induced IL-8 release was enhanced by treatment with PKC inhibitors (GF109203X and calphostin C) and PKC depletion, which completely inhibited PKC activity. Moreover, PKC inhibitors and PKC depletion increased extracellular signal-regulated kinase (ERK) activity and phosphorylation, but not calcium/calmodulin-dependent protein kinase II (CaMK II) activity, in response to H. pylori infection. PKC activated by H. pylori inhibited activation of ERK induced by H. pylori without affecting the CaMK II activity and negatively regulated IL-8 production in human gastric epithelial cells.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Adhesion Molecules / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gastric Mucosa / cytology
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology*
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / genetics
  • Helicobacter pylori / metabolism*
  • Humans
  • I-kappa B Kinase
  • Indoles / metabolism
  • Indoles / pharmacology
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / chemistry
  • Maleimides / metabolism
  • Maleimides / pharmacology
  • Methods
  • Naphthalenes / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Kinase C / pharmacology
  • Protein Serine-Threonine Kinases / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured

Substances

  • Cell Adhesion Molecules
  • Indoles
  • Interleukin-8
  • Maleimides
  • Naphthalenes
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • calphostin C
  • bisindolylmaleimide I
  • Tetradecanoylphorbol Acetate