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...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.展开更多
基金This work was supported by the Natural Science Foundation of Shanghai （04ZR14062） and by the Foundation for Excellent Young Investigator of Shanghai Jiao Tong University, School of Medicine, the National Key Program for Infectious Diseases of China （No. 2008ZX10004-002, No 2008ZX10004-009, No. 2009ZX10004-712）, and the Program of Shanghai Subject Chief Scientist （No. 09XD1402700）. We are grateful to Dr. Elizabeth Hohmann （Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School） for critical reading of the manuscript.
文摘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.
