H. pylori Escape Host Immunoreaction Through Inhibiting ILK Expression by VacA

• Published in: Cellular & molecular immunology 2009-06, Vol.6 (3), p.191-197
• Main Authors: Yuan, Jianping, Li, Ping, Tao, Jing, Shi, Xiaodong, Hu, Baoyu, Chen, Huabiao, Guo, Xiaokui
• Format: Article
• Language: English
• Subjects: Antibodies; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Biomedicine; Blotting, Western; eNOS; Expression vectors; Gastric mucosa; Gene expression; Gene Expression Regulation, Enzymologic; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - physiology; Host-Pathogen Interactions; Humans; ILK protein; Immune response; Immunology; Immunomodulation; Macrophages; Medical Microbiology; Microbiology; Monocytes; mRNA; Mutation; Nitric Oxide Synthase Type III - genetics; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal transduction; Transfection; U937 Cells; U937细胞; Up-Regulation; Vaccine; 信号转导通路; 免疫反应; 幽门螺旋杆菌; 幽门螺杆菌
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2009.26

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.