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Watson, D and Grimes, D (2019) Epoxyeicosatrienoic acids protect pancreatic beta cells against pro-inflammatory cytokine toxicity. Biochemical and Biophysical Research Communications, 520 (2). pp. 231-236.
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BBRC Grimes & Watson EET-Cytokines.docx - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (610kB) |
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 NFB 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 NFB 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 |
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Additional Information: | The final version of this accepted manuscript will be available at https://doi.org/10.1016/j.bbrc.2019.09.124 |
Uncontrolled Keywords: | Epoxyeicosatrienoic acids, EETs, dihydroxyeicosatrienoic acids, cytokines, diabetes, beta cells |
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: | 22 Mar 2021 16:00 |
URI: | https://eprints.keele.ac.uk/id/eprint/6973 |
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