Tang, T, Scambler, TE orcid.org/0000-0003-2468-0218, Smallie, T et al. (5 more authors) (2017) Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin E₂, dual specificity phosphatase 1 and tristetraprolin. Scientific Reports, 7. 4350. ISSN 2045-2322
Abstract
In many different cell types, pro-inflammatory agonists induce the expression of cyclooxygenase 2 (COX-2), an enzyme that catalyzes rate-limiting steps in the conversion of arachidonic acid to a variety of lipid signaling molecules, including prostaglandin E₂ (PGE₂). PGE₂ has key roles in many early inflammatory events, such as the changes of vascular function that promote or facilitate leukocyte recruitment to sites of inflammation. Depending on context, it also exerts many important anti-inflammatory effects, for example increasing the expression of the anti-inflammatory cytokine interleukin 10 (IL-10), and decreasing that of the pro-inflammatory cytokine tumor necrosis factor (TNF). The tight control of both biosynthesis of, and cellular responses to, PGE₂ are critical for the precise orchestration of the initiation and resolution of inflammatory responses. Here we describe evidence of a negative feedback loop, in which PGE₂ augments the expression of dual specificity phosphatase 1, impairs the activity of mitogen-activated protein kinase p38, increases the activity of the mRNA-destabilizing factor tristetraprolin, and thereby inhibits the expression of COX-2. The same feedback mechanism contributes to PGE₂-mediated suppression of TNF release. Engagement of the DUSP1-TTP regulatory axis by PGE₂ is likely to contribute to the switch between initiation and resolution phases of inflammation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Oct 2018 13:42 |
Last Modified: | 25 Jun 2023 21:33 |
Status: | Published |
Publisher: | Springer Nature |
Identification Number: | 10.1038/s41598-017-04100-1 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:137750 |