The phenyl-thiophenyl propenone RK-I-123 reduces the levels of reactive oxygen species and suppresses the activation of NF-κB and AP-1 and IL-8 expression in Helicobacter pylori-infected gastric epithelial AGS cells

Inflamm Res. 2013 Jul;62(7):689-96. doi: 10.1007/s00011-013-0621-4. Epub 2013 Apr 23.

Abstract

Objective: To investigate whether the phenyl-thiophenyl propenone RK-I-123 suppresses interleukin-8 (IL-8) expression and activation of mitogen-activated protein kinases (MAPKs) and transcription factors (nuclear factor-κB [NF-κB] and activator protein-1 [AP-1]) by reducing reactive oxygen species (ROS) levels in Helicobacter pylori-infected gastric epithelial cells.

Material: Helicobacter pylori in Korean isolates, human gastric epithelial AGS cells.

Treatment: AGS cells pretreated with or without RK-I-123 were cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1.

Methods: Reactive oxygen species and IL-8 levels were determined by dichlorofluorescein fluorescence and enzyme-linked immunosorbent assay. The IL-8 mRNA expression was analyzed by the real-time reverse transcription-polymerase chain reaction (RT-PCR). The MAPK and IκBα levels were determined by western blotting. The activation of NF-κB and AP-1 was determined by the electrophoretic mobility shift assay.

Results: Helicobacter pylori induced an increase in ROS and IL-8 expression and activation of MAPKs and transcription factors (NF-κB and AP-1) together with the degradation of IκBα in AGS cells, all of which were inhibited by RK-I-123.

Conclusions: The RK-I-123 suppressed the H. pylori-induced IL-8 expression and activation of MAPKs, NF-κB, and AP-1 by reducing ROS levels in AGS cells. The RK-I-123 may be a potential candidate for the treatment of H. pylori-induced gastric inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Chalcones / pharmacology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Gastric Mucosa / cytology
  • Gastric Mucosa / microbiology
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori
  • Humans
  • Interleukin-8 / immunology*
  • NF-kappa B / immunology
  • Reactive Oxygen Species / immunology
  • Thiophenes / pharmacology*
  • Transcription Factor AP-1 / immunology

Substances

  • 1-phenyl-3-(thiophen-2-yl)prop-2-en-1-one
  • Anti-Inflammatory Agents
  • Chalcones
  • Interleukin-8
  • NF-kappa B
  • Reactive Oxygen Species
  • Thiophenes
  • Transcription Factor AP-1