Effect of low oxygen concentration on activation of inflammation by Helicobacter pylori
Effect of low oxygen concentration on activation of inflammation by Helicobacter pylori
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DOI：
10.1016/j.bbrc.2021.04.123
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发表时间：
2021-05-14
影响因子：
3.1
通讯作者：
Suzuki, Toshihiko
中科院分区：
文献类型：
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作者：
Abass, Adiza;Okano, Tokuju;Suzuki, Toshihiko
人体胃肠道的特征在于高度独特的氧合曲线，其中氧浓度朝向下消化道降低，这在其他器官中没有发现。幽门螺杆菌所在粘膜的上皮细胞存在于相对低氧的环境中，氧分压（pO（2））低于58 mm Hg。然而，缺氧对H.幽门螺杆菌诱导的宿主免疫应答仍然难以捉摸。本实验研究了H. pylori在缺氧条件下，与常氧条件相比。我们的研究结果表明，caspase-1的激活和随后的IL-1 β的分泌显着增强在感染的巨噬细胞在1%的氧气下，与正常的20%的氧气浓度相比。H. pylori在需氧条件下比在微需氧条件下高3倍，并且细菌生长更依赖于CO2而不是氧。此外，我们观察到，缺氧诱导的细胞因子的产生以及HIF-1 α的积累都减少时，小鼠巨噬细胞与HIF-1 α抑制剂，KC 7 F2处理。缺氧可增强H. pylori中的HIF-1 α依赖性。在小鼠感染模型中，IL-1 β的产生也受到HIF-1 α抑制剂的影响，这表明HIF-1 α在感染H.幽门。我们的发现为低氧、H. pylori感染和炎症的关系，并揭示了H. pylori低氧分压可加重IL-1 β分泌。(C)2021爱思唯尔公司All rights reserved.
The gastrointestinal tract of the human body is characterized by a highly unique oxygenation profile, where the oxygen concentration decreases toward the lower tract, not found in other organs. The epithelial cells lining the mucosa where Helicobacter pylori resides exist in a relatively low oxygen environment with a partial pressure of oxygen (pO(2)) below 58 mm Hg. However, the contribution of hypoxia to H. pylori-induced host immune responses remains elusive. In this study, we investigated the inflammasome activation induced by H. pylori under hypoxic, compared with normoxic, conditions. Our results indicated that the activation of caspase-1 and the subsequent secretion of IL-1 beta were significantly enhanced in infected macrophages under 1% oxygen, compared with those under a normal 20% oxygen concentration. The proliferation of H. pylori under aerobic conditions was 3-fold higher than under microaerophilic conditions, and the bacterial growth was more dependent on CO2 than on oxygen. Also, we observed that hypoxia-induced cytokine production as well as HIF-1 alpha accumulation were both decreased when murine macrophages were treated with an HIF-1 alpha inhibitor, KC7F2. Furthermore, hypoxia enhanced the phagocytosis of H. pylori in an HIF-1 alpha-dependent manner. IL-1 beta production was also affected by the HIF-1 alpha inhibitor in a mouse infection model, suggesting the important role of HIF-1 alpha in the host defense system during infection with H. pylori. Our findings provide new insights into the intersection of low oxygen, H. pylori, and inflammation and disclosed how H. pylori under low oxygen tension can aggravate IL-1 beta secretion. (C) 2021 Elsevier Inc. All rights reserved.