Cyclopentenone Prostaglandins and Structurally Related Oxidized Lipid Species Instigate and Share Distinct Pro- and Anti-inflammatory Pathways.

Details

Serval ID
serval:BIB_FFBFA88A7B04
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cyclopentenone Prostaglandins and Structurally Related Oxidized Lipid Species Instigate and Share Distinct Pro- and Anti-inflammatory Pathways.
Journal
Cell reports
Author(s)
Muri J., Feng Q., Wolleb H., Shamshiev A., Ebner C., Tortola L., Broz P., Carreira E.M., Kopf M.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
31/03/2020
Peer-reviewed
Oui
Volume
30
Number
13
Pages
4399-4417.e7
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Oxidized lipids play a critical role in a variety of diseases with two faces: pro- and anti-inflammatory. The molecular mechanisms of this Janus-faced activity remain largely unknown. Here, we have identified that cyclopentenone-containing prostaglandins such as 15d-PGJ2 and structurally related oxidized phospholipid species possess a dual and opposing bioactivity in inflammation, depending on their concentration. Exposure of dendritic cells (DCs)/macrophages to low concentrations of such lipids before Toll-like receptor (TLR) stimulation instigates an anti-inflammatory response mediated by nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent inhibition of nuclear factor κB (NF-κB) activation and downstream targets. By contrast, high concentrations of such lipids upon TLR activation of DCs/macrophages result in inflammatory apoptosis characterized by mitochondrial depolarization and caspase-8-mediated interleukin (IL)-1β maturation independently of Nrf2 and the classical inflammasome pathway. These results uncover unexpected pro- and anti-inflammatory activities of physiologically relevant lipid species generated by enzymatic and non-enzymatic oxidation dependent on their concentration, a phenomenon known as hormesis.
Keywords
15d-PGJ2, IL-1β, Nrf2, OXPHOS, caspase-8, cyclopentenone prostaglandins, dendritic cells, inflammatory apoptosis, macrophages, oxidized phospholipids
Pubmed
Open Access
Yes
Create date
04/04/2020 15:35
Last modification date
11/06/2020 5:26
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