Hypoxia‐inducible factor (HIF)‐1α‐induced regulation of lung injury in pulmonary aspiration is mediated through NF‐kB

• DOI: 10.1096/fba.2021-00132
• Publication Date: 2021-12-30T06:59:50Z
• Authors: Madathilparambil ...; George Yalamanchili; Tejeshwar C. Rao; Sinan Aktay; Alex Kralovich; Yatrik M. Shah; Krishnan Raghaven...
• Keywords: CASP; Hypoxia; Hypoxia-Inducible Factors

Aspiration-induced lung injury is a common grievance encountered in the intensive care unit (ICU). It significant risk factor for improving ventilator-associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS). Hypoxia-inducible (HIF)-1α one of primary transcription factors responsible regulating cellular response to changes oxygen tension. Here, we sought determine role HIF-1α specifically type 2 alveolar epithelial cells generating inflammatory following acid particles (CASP) aspiration. Previous studies show HIF-1 α involved hypoxia-stimulated expression MCP-1 mice humans. The CASP was induced C57BL/6, ODD-Luc, (+/+) control, conditional knockout (HIF-1α (-/-) mice). Following an ODD mice, explanted organs were subjected IVIS imaging measure degree hypoxia. expression, BAL albumin, cytokines, histology measured CASP. In C57BL/6 level increased at 1 h after There significantly levels albumin cytokines ODD-Luc lungs given demonstrated synergistic increase leakage, pro-inflammatory worse injury. antibody neutralized showed reduced granuloma formation. NF-κB substantially compared mice. Our data collectively identify that upregulation depends on