[ODP-165] The effect of hypoxia on Helicobacter pylori induced inflammasome activation
The gastrointestinal tract within the human body is characterized by a highly unique oxygenation profile not found in other organs. The epithelial cells lining the mucosa where Helicobacter pylori resides exhibit a relatively low oxygen environment with a partial pressure of oxygen (pO2) below 58 mmHg. However, the contribution of hypoxia to Helicobacter pylori induced inflammasome activation remains elusive. We hypothesized that Helicobacter pylori induces elevated inflammasome activation in hypoxia compared to normoxic conditions. Our results indicated that Helicobacter pylori stimulated high secretion of IL-1β and caspase-1 under 1% oxygen compared to the normal 21% oxygen concentration. Helicobacter pylori growth in aerobic conditions was 3-fold higher than in microaerophilic conditions, and growth was more dependent on CO2 than oxygen. We showed that hypoxia mediates the secretion of IL-1β and caspase-1 in NLRP3 dependent manner. Also, we observed hypoxia-induced cytokine production as well as Hif-1α accumulation was decreased when murine macrophages were treated with Hif-1α inhibitor, KC7F2. Furthermore, hypoxia enhances phagocytosis of H. pylori in a Hif-1 dependent manner. This highlights the important role of Hif-1α in the host defense system during H. pylori infection. Our findings provide new insights into the intersection of low oxygen, H. pylori and inflammation.