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Exposure to normobaric hypoxia shapes the acute inflammatory response in human whole blood cells in vivo

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Název: Exposure to normobaric hypoxia shapes the acute inflammatory response in human whole blood cells in vivo
Autoři: Schönberger, Tina, Jakobs, Marie, Friedel, Anna-Lena, Hörbelt-Grünheidt, Tina, Tebbe, Bastian, Witzke, Oliver, Schedlowski, Manfred, Fandrey, Joachim
Zdroj: Pflugers Arch
Informace o vydavateli: Springer Science and Business Media LLC, 2024.
Rok vydání: 2024
Témata: Lipopolysaccharides, Male, Adult, Inflammation, 0301 basic medicine, 0303 health sciences, Medizin, Endotoxemia, Oxygen, 03 medical and health sciences, Female [MeSH], Hypoxia, Adult [MeSH], Humans [MeSH], In vivo, Endotoxemia/metabolism [MeSH], Lipopolysaccharides/pharmacology [MeSH], Oxygen/metabolism [MeSH], Whole blood cells, Hypoxia/immunology [MeSH], Lipopolysaccharides/toxicity [MeSH], Endotoxemia/immunology [MeSH], Human, Original Article, Male [MeSH], Inflammation/metabolism [MeSH], Hypoxia/metabolism [MeSH], Humans, Female
Popis: Cells of the immune defence, especially leukocytes, often have to perform their function in tissue areas that are characterized by oxygen deficiency, so-called hypoxia. Physiological hypoxia significantly affects leukocyte function and controls the innate and adaptive immune response mainly through transcriptional gene regulation via the hypoxia-inducible factors (HIFs). Multiple pathogens including components of bacteria, such as lipopolysaccharides (LPS) trigger the activation of leukocytes. HIF pathway activation enables immune cells to adapt to both hypoxic environments in physiological and inflammatory settings and modulates immune cell responses through metabolism changes and crosstalk with other immune-relevant signalling pathways. To study the mutual influence of both processes in vivo, we used a human endotoxemia model, challenging participants with an intravenous LPS injection post or prior to a 4-h stay in a hypoxic chamber with normobaric hypoxia of 10.5% oxygen. We analysed changes in gene expression in whole blood cells and determined inflammatory markers to unveil the crosstalk between both processes. Our investigations showed differentially altered gene expression patterns of HIF and target genes upon in vivo treatment with LPS and hypoxia. Further, we found evidence for effects of hypoxic priming upon inflammation in combination with immunomodulatory effects in whole blood cells in vivo. Our work elucidates the complex interplay of hypoxic and inflammatory HIF regulation in human immune cells and offers new perspectives for further clinical research.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-2013
0031-6768
DOI: 10.1007/s00424-024-02969-2
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38714572
https://repository.publisso.de/resource/frl:6519561
https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85192344901
https://doi.org/10.1007/s00424-024-02969-2
https://www.ncbi.nlm.nih.gov/pubmed/38714572
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....6fdae5c8e93784666003029cebd0b305
Databáze: OpenAIRE
Popis
Abstrakt:Cells of the immune defence, especially leukocytes, often have to perform their function in tissue areas that are characterized by oxygen deficiency, so-called hypoxia. Physiological hypoxia significantly affects leukocyte function and controls the innate and adaptive immune response mainly through transcriptional gene regulation via the hypoxia-inducible factors (HIFs). Multiple pathogens including components of bacteria, such as lipopolysaccharides (LPS) trigger the activation of leukocytes. HIF pathway activation enables immune cells to adapt to both hypoxic environments in physiological and inflammatory settings and modulates immune cell responses through metabolism changes and crosstalk with other immune-relevant signalling pathways. To study the mutual influence of both processes in vivo, we used a human endotoxemia model, challenging participants with an intravenous LPS injection post or prior to a 4-h stay in a hypoxic chamber with normobaric hypoxia of 10.5% oxygen. We analysed changes in gene expression in whole blood cells and determined inflammatory markers to unveil the crosstalk between both processes. Our investigations showed differentially altered gene expression patterns of HIF and target genes upon in vivo treatment with LPS and hypoxia. Further, we found evidence for effects of hypoxic priming upon inflammation in combination with immunomodulatory effects in whole blood cells in vivo. Our work elucidates the complex interplay of hypoxic and inflammatory HIF regulation in human immune cells and offers new perspectives for further clinical research.
ISSN:14322013
00316768
DOI:10.1007/s00424-024-02969-2