Keith Wilson
Faculty Member
Last active: 8/13/2019

Haem oxygenase-1 inhibits phosphorylation of the Helicobacter pylori oncoprotein CagA in gastric epithelial cells.

Gobert AP, Verriere T, de Sablet T, Peek RM, Chaturvedi R, Wilson KT
Cell Microbiol. 2013 15 (1): 145-56

PMID: 23051580 · PMCID: PMC3524338 · DOI:10.1111/cmi.12039

The cytotoxin-associated gene A protein (CagA) plays a pivotal role in the aetiology of Helicobacter pylori-associated gastric diseases. CagA is injected into the cytoplasm of host cells by a type IV secretion system, and is phosphorylated on tyrosine residues by the host enzyme c-Src. We previously reported that the enzyme haem oxygenase-1 (HO-1) inhibits IL-8 secretion by H. pylori-infected cells. However, the cellular mechanism by which HO-1 regulates the innate immune function of infected cells remains unknown. We now show that nitric oxide and haemin, two inducers of HO-1, decrease the level of phosphorylated CagA (p-CagA) in H. pylori-infected gastric epithelial cells and this is blocked by either pharmacological inhibition of HO-1 or siRNA knockdown of hmox-1. Moreover, forced expression of HO-1 by transfection of a plasmid expressing hmox-1 also results in a strong attenuation of CagA phosphorylation. This occurs through the inhibition of H. pylori-induced c-Src phosphorylation/activation by HO-1. Consequently, H. pylori-induced cytoskeletal rearrangements and activation of the pro-inflammatory response mediated by p-CagA are inhibited in HO-1-expressing cells. These data highlight a mechanism by which the innate immune response of the host can restrict the pathogenicity of H. pylori by attenuating CagA phosphorylation in gastric epithelial cells.

© 2012 Blackwell Publishing Ltd.

MeSH Terms (11)

Antigens, Bacterial Bacterial Proteins Cell Line Epithelial Cells Helicobacter pylori Heme Oxygenase-1 Host-Pathogen Interactions Humans Oncogene Proteins Phosphorylation Protein Processing, Post-Translational

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