Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3-dependent COX-2 expression both in vitro and in vivo. STAT3 upre- gulats COX-2 by binding to and increasing the activity of COX-2 promoter. COX-2 in turn regulates IL-6=STAT3 signaling under basal conditions and during H. pylori infection. These findings suggest that a positive feedback loop between STAT3 and COX- 2 exists in the basal condition and H. pylori infectious condition. Immunohistochemical staining revealed that H. pylori-posi- tive gastritis tissues exhibited markedly higher levels of pSTAT3 Tyr705 than H. pylori-negative ones. High pSTAT3 Tyr705 levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3 Tyr705 may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3=pSTAT3 Tyr705 levels and COX-2 expression was identi- fied in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effec- tive therapy of gastric cancer

第一署名医院：仁济医院