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Discovery of aspirin-triggered eicosanoid-like mediators in a Drosophila metainflammation blood tumor model.


ABSTRACT: Epidemiologic studies have linked the use of aspirin to a decline in chronic inflammation that underlies many human diseases, including some cancers. Aspirin reduces the levels of cyclooxygenase-mediated pro-inflammatory prostaglandins, promotes the production of pro-resolution molecules, and triggers the production of anti-inflammatory electrophilic mono-oxygenated (EFOX) lipid mediators. We investigated the effects of aspirin in fruit fly models of chronic inflammation. Ectopic Toll/NF-?B and JAK/STAT signaling in mutant D. melanogaster results in overproliferation of hematopoietic blood progenitors resulting in the formation of granuloma-like tumors. Ectopic JAK-STAT signaling also leads to metabolic inflammation. We report that aspirin-treated mutant flies experience reduction in metabolic inflammation, mitosis, ectopic immune signaling, and macrophage infiltration. Moreover, these flies synthesize 13-HODE, and aspirin triggers 13-oxoODE (13-EFOX-L2) production. Providing the precursor of 13-HODE, linoleic acid, or performing targeted knockdown of the transcription factor STAT in inflammatory blood cells, boosts 13-EFOX-L2 levels while decreasing metabolic inflammation. Thus, hematopoietic cells regulate metabolic inflammation in flies, and their effects can be reversed by pharmaceutical or dietary intervention, suggesting deep phylogenetic conservation in the ability of animals to resolve inflammation and repair tissue damage. These findings can help identify novel treatment targets in humans.

SUBMITTER: Panettieri S 

PROVIDER: S-EPMC7033724 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Discovery of aspirin-triggered eicosanoid-like mediators in a <i>Drosophila</i> metainflammation blood tumor model.

Panettieri Silvio S   Paddibhatla Indira I   Chou Jennifer J   Rajwani Roma R   Moore Rebecca S RS   Goncharuk Tamara T   John George G   Govind Shubha S   Govind Shubha S  

Journal of cell science 20191028 5


Epidemiologic studies have linked the use of aspirin to a decline in chronic inflammation that underlies many human diseases, including some cancers. Aspirin reduces the levels of cyclooxygenase-mediated pro-inflammatory prostaglandins, promotes the production of pro-resolution molecules, and triggers the production of anti-inflammatory electrophilic mono-oxygenated (EFOX) lipid mediators. We investigated the effects of aspirin in fruit fly models of chronic inflammation. Ectopic Toll/NF-κB and  ...[more]

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