Lewis, A. and Elks, P.M. orcid.org/0000-0003-1683-0749 (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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | COX–cyclooxygenase; HIF–hypoxia inducible factor; TNF–tumour necrosis factor; hypoxia; in vivo; macrophage; prostaglandin; zebrafish |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 105570/Z/14/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Nov 2019 10:15 |
Last Modified: | 25 Jun 2023 22:02 |
Status: | Published |
Publisher: | Frontiers Media |
Refereed: | Yes |
Identification Number: | 10.3389/fimmu.2019.02321 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:152924 |