Effect of low oxygen concentration on activation of inflammation by Helicobacter pylori

Biochem Biophys Res Commun. 2021 Jun 30;560:179-185. doi: 10.1016/j.bbrc.2021.04.123. Epub 2021 May 14.

Abstract

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 (pO2) 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-1β 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-1α accumulation were both decreased when murine macrophages were treated with an HIF-1α inhibitor, KC7F2. Furthermore, hypoxia enhanced the phagocytosis of H. pylori in an HIF-1α-dependent manner. IL-1β production was also affected by the HIF-1α inhibitor in a mouse infection model, suggesting the important role of HIF-1α 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-1β secretion.

Keywords: HIF-1α; Helicobacter pylori; Hypoxia; Inflammasome; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cells, Cultured
  • Cytokines / metabolism
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / metabolism
  • Helicobacter pylori / physiology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Inflammasomes / metabolism*
  • Inflammation / immunology
  • Macrophages / physiology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology
  • Phagocytosis

Substances

  • Cytokines
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse