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Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells

Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells
Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells
Alpha-linolenic acid (ALA) and linoleic acid (LA) are precursors for longer-chain more unsaturated fatty acids and for lipid signalling molecules that may influence inflammatory processes through a variety of mechanisms. The actions of LA and ALA may be divergent and interdependent. The aim of this study was to investigate the incorporation and metabolism of ALA and LA in cultured in EA.hy926 endothelial cells and the production of inflammatory mediators (VEGF, RANTES, ICAM-1, MCP-1, IL-6 and IL-8) by these cells when exposed to different concentrations of ALA, LA and ratios of LA:ALA. Human endothelial cells were cultured with either culture medium or culture medium supplemented with ALA, LA or various ratios of LA:ALA (1:4, 1:1, 4:1, 9:1 or 19:1) followed by 24 h TNF-α stimulation; the total concentration of ALA plus LA was kept constant at 100 μM. The incorporation and metabolism of ALA and LA was measured using gas chromatography. The production of inflammatory mediators in the supernatant was assessed using a Luminex Multi-Analyte kit. Both ALA and LA were incorporated and metabolised by the endothelial cells. Cells incubated with ALA had a statistically significantly lower production of VEGF, RANTES, ICAM-1, MCP-1 and IL-6 compared to cells incubated without additional ALA. LA was not found to exert pro-inflammatory effects. Cells incubated with low LA:ALA ratios had lower production of VEGF, RANTES, MCP-1 and IL-6 when compared with a LA:ALA ratio of 19:1. These findings suggest that a low LA:ALA ratio exerts anti-inflammatory effects by lowering the production VEGF, RANTES, ICAM-1, MCP-1 and IL-6 in TNF-α stimulated endothelial cells compared to a high ratio. These effects were likely mediated by ALA, but LA may also possess some anti-inflammatory effects.
0952-3278
1-8
Bork, Christian Sørensen
740e1b22-fc72-4145-ba9b-994ae59bb5e7
Baker, Ella
7cd5b762-d7d7-4584-b9a7-dba555085440
Lundbye-Christensen, Søren
43e057cb-004a-4533-b235-cf2739e04ecb
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Bork, Christian Sørensen
740e1b22-fc72-4145-ba9b-994ae59bb5e7
Baker, Ella
7cd5b762-d7d7-4584-b9a7-dba555085440
Lundbye-Christensen, Søren
43e057cb-004a-4533-b235-cf2739e04ecb
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6

Bork, Christian Sørensen, Baker, Ella, Lundbye-Christensen, Søren, Miles, Elizabeth and Calder, Philip (2019) Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells. Prostaglandins, Leukotrienes and Essential Fatty Acids, 141, 1-8. (doi:10.1016/j.plefa.2018.12.001).

Record type: Article

Abstract

Alpha-linolenic acid (ALA) and linoleic acid (LA) are precursors for longer-chain more unsaturated fatty acids and for lipid signalling molecules that may influence inflammatory processes through a variety of mechanisms. The actions of LA and ALA may be divergent and interdependent. The aim of this study was to investigate the incorporation and metabolism of ALA and LA in cultured in EA.hy926 endothelial cells and the production of inflammatory mediators (VEGF, RANTES, ICAM-1, MCP-1, IL-6 and IL-8) by these cells when exposed to different concentrations of ALA, LA and ratios of LA:ALA. Human endothelial cells were cultured with either culture medium or culture medium supplemented with ALA, LA or various ratios of LA:ALA (1:4, 1:1, 4:1, 9:1 or 19:1) followed by 24 h TNF-α stimulation; the total concentration of ALA plus LA was kept constant at 100 μM. The incorporation and metabolism of ALA and LA was measured using gas chromatography. The production of inflammatory mediators in the supernatant was assessed using a Luminex Multi-Analyte kit. Both ALA and LA were incorporated and metabolised by the endothelial cells. Cells incubated with ALA had a statistically significantly lower production of VEGF, RANTES, ICAM-1, MCP-1 and IL-6 compared to cells incubated without additional ALA. LA was not found to exert pro-inflammatory effects. Cells incubated with low LA:ALA ratios had lower production of VEGF, RANTES, MCP-1 and IL-6 when compared with a LA:ALA ratio of 19:1. These findings suggest that a low LA:ALA ratio exerts anti-inflammatory effects by lowering the production VEGF, RANTES, ICAM-1, MCP-1 and IL-6 in TNF-α stimulated endothelial cells compared to a high ratio. These effects were likely mediated by ALA, but LA may also possess some anti-inflammatory effects.

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Accepted/In Press date: 11 December 2018
e-pub ahead of print date: 12 December 2018
Published date: February 2019

Identifiers

Local EPrints ID: 426864
URI: https://eprints.soton.ac.uk/id/eprint/426864
ISSN: 0952-3278
PURE UUID: 538ece18-1b5e-4bf6-a72a-8bb6276bac3b
ORCID for Elizabeth Miles: ORCID iD orcid.org/0000-0002-8643-0655

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Date deposited: 14 Dec 2018 17:30
Last modified: 14 Mar 2019 01:55

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Author: Christian Sørensen Bork
Author: Ella Baker
Author: Søren Lundbye-Christensen
Author: Elizabeth Miles ORCID iD
Author: Philip Calder

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