Virulence factor cytotoxin-associated gene A in Helicobacter pylori is downregulated by interferon-γ in vitro.
Helicobacter pylori-infected gastric mucosa is characterized by high levels of interferon-γ (IFN-γ), but whether the high level of IFN-γ regulates the virulence of H. pylori is unclear. Here, we characterized the response of H. pylori to IFN-γ and found by indirect immunofluorescence that IFN-γ can bind to H. pylori. The binding resulted in the altered expression of 14 proteins, including the virulence factor, cytotoxin-associated gene A (CagA), whose expression was downregulated. The transcription and translation of CagA downregulated by IFN-γ was further confirmed by reverse transcriptase-PCR and Western blot analysis. We co-cultured the human gastric cancer cell line AGS with H. pylori exposed to IFN-γ; both phosphorylated CagA and nonphosphorylated CagA in AGS cells were downregulated by IFN-γ, and the proportion of cells with the 'hummingbird' phenotype was also decreased. Thus, IFN-γ can help control H. pylori infection indirectly through the virulence factor CagA.
Department of Microbiology and Key Lab for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, Shandong, China.
Yinghui
Y
Zhao
Yabin
Y
Zhou
Yundong
Y
Sun
Ailian
A
Yu
Han
H
Yu
Wenjuan
W
Li
Zhifang
Z
Liu
Jiping
J
Zeng
Xi
X
Li
Chunyan
C
Chen
Jihui
J
Jia
D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D007371:Interferon-gamma