Blockage of HSP 90 modulates Helicobacter pylori-induced IL-8 productions through the inactivation of transcriptional factors of AP-1 and NF-kappaB

Biochem Biophys Res Commun. 2004 Jul 30;320(3):816-24. doi: 10.1016/j.bbrc.2004.05.214.

Abstract

Helicobacter pylori infection leads to significant inflammations in the gastric mucosa, which is closely associated with development of gastric cancer. Heat shock protein 90 (HSP 90) has been revealed to be critical for intracellular signaling that participates in inflammatory response as well as carcinogenesis. In this study, we investigated a regulatory role of HSP 90 in H. pylori-induced IL-8 production. Our results showed that H. pylori stimulated significant phosphorylation of HSP 90 and the phosphorylation was diminished by administration of HSP 90 inhibitor, geldanamycin (GA). Treatment of GA completely inhibited H. pylori-induced IL-8 production due to deactivation of ERK1/2 and NF-kappaB. These results subsequently lead to inactivation of AP-1 and NF-kappaB, which are known to be major transcriptional factors of IL-8. Our data provide important insights that HSP 90 is involved as a crucial regulator in H. pylori-induced IL-8 production and its inhibitor could be potentially used for the inhibition of H. pylori-provoked inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones
  • Cell Line
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / microbiology
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism*
  • Helicobacter Infections / metabolism*
  • Helicobacter pylori / drug effects
  • Humans
  • Interleukin-8 / biosynthesis*
  • Lactams, Macrocyclic
  • NF-kappa B / metabolism*
  • Quinones / pharmacology*
  • Transcription Factor AP-1 / metabolism*
  • Transcriptional Activation / drug effects

Substances

  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Interleukin-8
  • Lactams, Macrocyclic
  • NF-kappa B
  • Quinones
  • Transcription Factor AP-1
  • geldanamycin