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
To explore the mechanism of epilepsy induced by IL-1β and IL-6, the changes of glutamic acid (Glu) and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1β or IL-6 were st...To explore the mechanism of epilepsy induced by IL-1β and IL-6, the changes of glutamic acid (Glu) and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1β or IL-6 were studied. Rats were randomly divided into 3 groups: control group (intracerebroventricular injection (icv) of NS), IL-1β group (icv injection of IL-1β) and IL-6 group (i.c.v. injection of IL-6). 120 min after the icv injection of reagents of IL-1β or IL-6, behavioral changes were observed and Glu and GABA in the cerebral cortex and hippocampus were examined by means of immunohistochemistry. Our results showed that no seizure developed in the control group, while moderate seizure was observed in IL-1β group and IL-6 group. Compared with the controls, the immunoreaction of Glu was significantly increased, while GABA was obviously decreased in IL-1β group and IL-6 group after 120 min. Our study suggested that the IL-1β and IL-6 might promote and induce epilepsy by increasing Glu and decreasing GABA in the cerebral cortex and hippocampus.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.
基金This project was supported by a grant from the NationalNatural Science Foundation of China (No .2001ABB142) .
文摘To explore the mechanism of epilepsy induced by IL-1β and IL-6, the changes of glutamic acid (Glu) and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1β or IL-6 were studied. Rats were randomly divided into 3 groups: control group (intracerebroventricular injection (icv) of NS), IL-1β group (icv injection of IL-1β) and IL-6 group (i.c.v. injection of IL-6). 120 min after the icv injection of reagents of IL-1β or IL-6, behavioral changes were observed and Glu and GABA in the cerebral cortex and hippocampus were examined by means of immunohistochemistry. Our results showed that no seizure developed in the control group, while moderate seizure was observed in IL-1β group and IL-6 group. Compared with the controls, the immunoreaction of Glu was significantly increased, while GABA was obviously decreased in IL-1β group and IL-6 group after 120 min. Our study suggested that the IL-1β and IL-6 might promote and induce epilepsy by increasing Glu and decreasing GABA in the cerebral cortex and hippocampus.
