Keith Wilson
Faculty Member
Last active: 11/2/2019

Disruption of nitric oxide signaling by Helicobacter pylori results in enhanced inflammation by inhibition of heme oxygenase-1.

Gobert AP, Asim M, Piazuelo MB, Verriere T, Scull BP, de Sablet T, Glumac A, Lewis ND, Correa P, Peek RM, Chaturvedi R, Wilson KT
J Immunol. 2011 187 (10): 5370-9

PMID: 21987660 · PMCID: PMC3208050 · DOI:10.4049/jimmunol.1102111

A strong cellular cross-talk exists between the pathogen Helicobacter pylori and high-output NO production. However, how NO and H. pylori interact to signal in gastric epithelial cells and modulate the innate immune response is unknown. We show that chemical or cellular sources of NO induce the anti-inflammatory effector heme oxygenase-1 (HO-1) in gastric epithelial cells through a pathway that requires NF-κB. However, H. pylori decreases NO-induced NF-κB activation, thereby inhibiting HO-1 expression. This inhibitory effect of H. pylori results from activation of the transcription factor heat shock factor-1 by the H. pylori virulence factor CagA and by the host signaling molecules ERK1/2 and JNK. Consistent with these findings, HO-1 is downregulated in gastric epithelial cells of patients infected with cagA(+) H. pylori but not in gastric epithelial cells of patients infected with cagA(-) H. pylori. Enhancement of HO-1 activity in infected cells or in H. pylori-infected mice inhibits chemokine generation and reduces inflammation. These data define a mechanism by which H. pylori favors its own pathogenesis by inhibiting HO-1 induction through the action of CagA.

MeSH Terms (17)

Animals Antigens, Bacterial Bacterial Proteins Cell Line Cell Line, Transformed Gastric Mucosa Helicobacter pylori Heme Oxygenase-1 Humans Inflammation Mediators Male Mice Mice, Inbred C57BL Nitric Oxide Signal Transduction Up-Regulation Virulence Factors

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