PUBLICATION
Hypoxia Induces Macrophage tnfa Expression via Cyclooxygenase and Prostaglandin E2 in vivo
- Authors
- Lewis, A., Elks, P.M.
- ID
- ZDB-PUB-191016-3
- Date
- 2019
- Source
- Frontiers in immunology 10: 2321 (Journal)
- Registered Authors
- Elks, Philip
- Keywords
- COX–cyclooxygenase, HIF–hypoxia inducible factor, TNF–tumour necrosis factor, hypoxia, in vivo, macrophage, prostaglandin, zebrafish
- MeSH Terms
-
- Animals
- Cell Line
- Dinoprostone/metabolism*
- Humans
- Hypoxia/metabolism*
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Leukocytes, Mononuclear/metabolism*
- Macrophages/metabolism*
- Prostaglandin-Endoperoxide Synthases/metabolism*
- Tumor Necrosis Factor-alpha/metabolism*
- Zebrafish
- PubMed
- 31611882 Full text @ Front Immunol
Citation
Lewis, A., Elks, P.M. (2019) Hypoxia Induces Macrophage tnfa Expression via Cyclooxygenase and Prostaglandin E2 in vivo. Frontiers in immunology. 10:2321.
Abstract
Macrophage phenotypes are poorly characterized in disease systems in vivo. Appropriate macrophage activation requires complex coordination of local microenvironmental cues and cytokine signaling. If the molecular mechanisms underpinning macrophage activation were better understood, macrophages could be pharmacologically tuned during disease situations. Here, using zebrafish tnfa:GFP transgenic lines as in vivo readouts, we show that physiological hypoxia and stabilization of Hif-1α promotes macrophage tnfa expression. We demonstrate a new mechanism of Hif-1α-induced macrophage tnfa expression via a cyclooxygenase/prostaglandin E2 axis. These findings uncover a macrophage HIF/COX/TNF axis that links microenvironmental cues to macrophage phenotype, with important implications during inflammation, infection, and cancer, where hypoxia is a common microenvironmental feature and where cyclooxygenase and TNF are major mechanistic players.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping