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Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity.

ABSTRACT: Neuroinflammation driven primarily by microglia directly contributes to neuronal death in many neurodegenerative diseases. Classical anti-inflammatory approaches aim to suppress pro-inflammatory mediator production, but exploitation of inflammatory resolution may also be of benefit. A key driver of peripheral inflammatory resolution, formyl peptide receptor 2 (Fpr2), is expressed by microglia, but its therapeutic potential in neurodegeneration remains unclear. Here, we studied whether targeting of Fpr2 could reverse inflammatory microglial activation induced by the potent bacterial inflammogen lipopolysaccharide (LPS). Exposure of murine primary or immortalised BV2 microglia to LPS triggered pro-inflammatory phenotypic change and activation of ROS production, effects significantly attenuated by subsequent treatment with the Fpr2 agonist C43. Mechanistic studies showed C43 to act through p38 MAPK phosphorylation and reduction of LPS-induced NFκB nuclear translocation via prevention of IκBα degradation. Here, we provide proof-of-concept data highlighting Fpr2 as a potential target for control of microglial pro-inflammatory activity, suggesting that it may be a promising therapeutic target for the treatment of neuroinflammatory disease.

SUBMITTER: Wickstead ES

PROVIDER: S-EPMC10649357 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity.

Wickstead Edward S ES Elliott Bradley T BT Pokorny Sarah S Biggs Christopher C Getting Stephen J SJ McArthur Simon S

International journal of molecular sciences 20231106 21

Neuroinflammation driven primarily by microglia directly contributes to neuronal death in many neurodegenerative diseases. Classical anti-inflammatory approaches aim to suppress pro-inflammatory mediator production, but exploitation of inflammatory resolution may also be of benefit. A key driver of peripheral inflammatory resolution, formyl peptide receptor 2 (Fpr2), is expressed by microglia, but its therapeutic potential in neurodegeneration remains unclear. Here, we studied whether targeting ...[more]

PMID: 37958978

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Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity.

Publications

Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity.

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