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

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.

Citation

Watson. (2019). Epoxyeicosatrienoic acids protect pancreatic beta cells against pro-inflammatory cytokine toxicity. Biochemical and Biophysical Research Communications, 231-236. https://doi.org/10.1016/j.bbrc.2019.09.124

• Acceptance Date: Sep 27, 2019
• Publication Date: Dec 3, 2019
• 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