H. pylori escape host immunoreaction through inhibiting ILK expression by VacA.
Helicobacter pylori (H. pylori) persistently colonizes the gastric mucosa despite a vigorous immune response. Vacuolating cytotoxin secreted by H. pylori has turned out to be a potent immunomodulatory toxin, but the signal transduction pathways involved has not been studied in macrophages. We observed in this study that vacA-deficient H. pylori induced significantly higher expression of integrin-linked kinase (ILK) and endothelial nitric oxygen synthase (eNOS), and significantly more production of reactive oxygen species (ROS) in monocyte/macrophage-like U937 cells, as compared with isogenic vacA+ H. pylori. The expression of eNOS mRNA in U937 cells overexpressing ILK was markedly increased compared with those transfected with empty vectors. Thus, vacA-deficient H. pylori appears to upregulate ILK expression, which modulates the expression of eNOS and as a result, stimulates the production of ROS. It is VacA that prevents such a process by inhibiting ILK expression, helping H. pylori escape host immunoreaction. This mechanism explains, at least in part, persistent infection of H. pylori in the stomach.
Yuan
Jianping
J
Department of Medical Microbiology and Parasitology, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, China. microbiology@sjtu.edu.cn
Li
Ping
P
Tao
Jing
J
Shi
Xiaodong
X
Hu
Baoyu
B
Chen
Huabiao
H
Guo
Xiaokui
X
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015971:Gene Expression Regulation, Enzymologic; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D020298:U937 Cells; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
D001426:Bacterial Proteins; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000099200:Scaffold Protein ILK; C074689:VacA protein, Helicobacter pylori