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Epoxyeicosatrienoic acids protect pancreatic beta cells against pro-inflammatory cytokine toxicity

Watson

Authors

Watson



Abstract

Pro-inflammatory cytokines contribute to pancreatic beta cell death in the pathogenesis of type 1 diabetes mellitus (DM). Cytochrome P450-derived epoxyeicosatrienoic acids (EETs), produced by selective epoxidation of arachidonic acid, display anti-inflammatory activity in numerous disease models, in part through inhibition of NF?B activity. No studies have directly assessed their roles in cellular models of pancreatic beta cell death and therefore we aimed to investigate the cytoprotective effects of the EET isomers 8(9)-, 11(12)- and 14(15)-EET and their corresponding vicinal diols (dihydroxyeicosatrienoic acids, DHETs) in a model of pro-inflammatory cytokine-toxicity using the rat pancreatic beta cell line BRIN-BD11. Co-treatment of cells with a cocktail of pro-inflammatory cytokines (IL-1ß, IFN? and TNFa) caused a marked increase in caspase activation and a reduction in cell viability, effects attenuated by inclusion of each EET; this was also associated with a reduction in cytokine-induced NF?B activation and nitrite accumulation. Surprisingly, of the DHET derivatives of EETs, 8(9)-DHET conferred similar protective effects against cytokine-induced caspase activation. This data therefore highlights a novel role of EETs and a surprising activity of 8(9)-DHET in attenuating cytokine-toxicity in pancreatic beta cells.

Acceptance Date Sep 27, 2019
Publication Date Dec 3, 2019
Publicly Available Date Mar 28, 2024
Journal Biochemical and Biophysical Research Communications
Print ISSN 0006-291X
Publisher Elsevier
Pages 231-236
DOI https://doi.org/10.1016/j.bbrc.2019.09.124
Keywords Epoxyeicosatrienoic acids, EETs, dihydroxyeicosatrienoic acids, cytokines, diabetes, beta cells
Publisher URL https://doi.org/10.1016/j.bbrc.2019.09.124