Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin E 2 , dual specificity phosphatase 1 and tristetraprolin

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 E 2 (PGE 2 ). PGE 2 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, PGE 2 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 PGE 2 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 PGE 2 -mediated suppression of TNF release. Engagement of the DUSP1-TTP regulatory axis by PGE 2 is likely to contribute to the switch between initiation and resolution phases of inflammation.

Publication DOI: https://doi.org/10.1038/s41598-017-04100-1
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Additional Information: 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/.
Uncontrolled Keywords: General
Publication ISSN: 2045-2322
Last Modified: 18 Mar 2024 08:32
Date Deposited: 29 Aug 2019 15:29
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.nat ... 598-017-04100-1 (Publisher URL)
PURE Output Type: Article
Published Date: 2017-06-28
Accepted Date: 2017-05-09
Authors: Tang, Tina
Scambler, Thomas E.
Smallie, Tim
Cunliffe, Helen E.
Ross, Ewan A. (ORCID Profile 0000-0001-5733-9361)
Rosner, Dalya R.
O'Neil, John D.
Clark, Andrew R.

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