Watson, D and Grimes, D (2019) Epoxyeicosatrienoic acids protect pancreatic beta cells against pro-inflammatory cytokine toxicity. Biochemical and Biophysical Research Communications. (In Press)

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BBRC Grimes & Watson EET-Cytokines.docx - Accepted Version
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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-1β, IFNγ and TNFα) 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.

Item Type: Article
Additional Information: The final version of this accepted manuscript will be available at https://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 04 Oct 2019 15:01
Last Modified: 11 Oct 2019 13:38
URI: http://eprints.keele.ac.uk/id/eprint/6973

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