Open AccessHaem oxygenase‐1 inhibits phosphorylation of the H elicobacter pylori oncoprotein CagA in gastric epithelial cells
Author(s) -
Gobert Alain P.,
Verriere Thomas,
Sablet Thibaut,
Peek Richard M.,
Chaturvedi Rupesh,
Wilson Keith T.
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12039
Subject(s) - caga , biology , helicobacter pylori , phosphorylation , secretion , transfection , innate immune system , tyrosine phosphorylation , immune system , gene knockdown , microbiology and biotechnology , cell culture , immunology , biochemistry , virulence , gene , genetics
Summary The cytotoxin‐associated gene A protein ( CagA ) plays a pivotal role in the aetiology of H elicobacter 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‐ S rc. 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‐ S rc 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.