Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells

Askari, A A; Thomson, S; Edin, M L; Lih, F B; Zeldin, D C; Bishop-Bailey, D

Abstract

The roles of CYP lipid-metabolizing pathways in endothelial cells are poorly understood. Human endothelial cells expressed CYP2J2 and soluble epoxide hydrolase (sEH) mRNA and protein. The TLR-4 agonist LPS (1 μg/ml; 24 h) induced CYP2J2 but not sEH mRNA and protein. LC–MS/MS analysis of the stable commonly used human endothelial cell line EA.Hy926 showed active epoxygenase and epoxide hydrolase activity: with arachidonic acid (stable epoxide products 5,6-DHET, and 14,15-DHET), linoleic acid (9,10-EPOME and 12,13-EPOME and their stable epoxide hydrolase products 9,10-DHOME and 12,13-DHOME), docosahexaenoic acid (stable epoxide hydrolase product 19,20-DiHDPA) and eicosapentaenoic acid (stable epoxide hydrolase product 17,18-DHET) being formed. Inhibition of epoxygenases using either SKF525A or MS-PPOH induced TNFα release, but did not affect LPS, IL-1β, or phorbol-12-myristate-13-acetate (PMA)-induced TNFα release. In contrast, inhibition of soluble epoxide hydrolase by AUDA or TPPU inhibited basal, LPS, IL-1β and PMA induced TNFα release, and LPS-induced NFκB p65 nuclear translocation. In conclusion, human endothelial cells contain a TLR-4 regulated epoxygenase CYP2J2 and metabolize linoleic acid > eicosapentaenoic acid > arachidonic acid > docosahexaenoic acid to products with anti-inflammatory activity.

Citation

Askari, A. A., Thomson, S., Edin, M. L., Lih, F. B., Zeldin, D. C., & Bishop-Bailey, D. (in press). Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells. Biochemical and Biophysical Research Communications, 446(2), 633-637. https://doi.org/10.1016/j.bbrc.2014.03.020

• Journal Article Type: Article
• Acceptance Date: Mar 1, 2014
• Deposit Date: Nov 11, 2014
• Publicly Available Date: Nov 21, 2020
• Journal: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• Print ISSN: 0006-291X
• Publisher: Academic Press
• Peer Reviewed: Peer Reviewed
• Volume: 446
• Issue: 2
• Pages: 633-637
• DOI: https://doi.org/10.1016/j.bbrc.2014.03.020
• Public URL: https://rvc-repository.worktribe.com/output/1405888