Helicobacter pylori infection activates NF-kappaB signaling pathway to induce iNOS and protect human gastric epithelial cells from apoptosis

Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1171-80. doi: 10.1152/ajpgi.00502.2002. Epub 2003 Aug 14.

Abstract

Helicobacter pylori infection induces apoptosis and inducible nitric oxide synthase (iNOS) expression in gastric epithelial cells. In this study, we investigated the effects of NF-kappaB activation and iNOS expression on apoptosis in H. pylori-infected gastric epithelial cells. The suppression of NF-kappaB significantly increased caspase-3 activity and apoptosis in H. pylori-infected MKN-45 and Hs746T gastric epithelial cell lines as well as primary gastric epithelial cells. An NF-kappaB signaling pathway via NF-kappaB-inducing kinase and IkappaB kinase-beta activation was found to be involved in the inhibition of apoptosis in H. pylori-infected gastric epithelial cells. In gastric epithelial cells transfected with retrovirus containing IkappaBalpha superrepressor, iNOS mRNA and protein levels were reduced, indicating that H. pylori infection induced the expression of iNOS by activating NF-kappaB. Moreover, a NO donor, S-nitroso-N-acetylpenicillamine (100 microM), decreased caspase-3 activity and apoptosis in NF-kappaB-suppressed cells infected with H. pylori. These results suggest that NF-kappaB activation may play a role in protecting gastric epithelial cells from H. pylori-induced apoptosis by upregulating endogenous iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspase 3
  • Caspases / metabolism
  • Cell Line
  • Enzyme Activation
  • Enzyme Induction
  • Epithelial Cells
  • Gastric Mucosa / physiopathology*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / physiopathology*
  • Helicobacter pylori*
  • Humans
  • I-kappa B Kinase
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • NF-kappaB-Inducing Kinase
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction*

Substances

  • NF-kappa B
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • CASP3 protein, human
  • Caspase 3
  • Caspases