Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells
Polyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence indicates that immune cell activation involves endogenous PUFA synthesis, but this has not been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and activated peripheral blood mononu...
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doaj-a2774fddb8d8462ab9ce9cd70c2c50362020-11-25T00:37:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00432339683Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear CellsCharlene M. Sibbons0Charlene M. Sibbons1Nicola A. Irvine2J. Eduardo Pérez-Mojica3Philip C. Calder4Karen A. Lillycrop5Barbara A. Fielding6Graham C. Burdge7Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, United KingdomDepartment of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United KingdomAcademic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, United KingdomAcademic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, United KingdomNIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, Hampshire, United KingdomCentre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, Hampshire, United KingdomDepartment of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United KingdomAcademic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, United KingdomPolyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence indicates that immune cell activation involves endogenous PUFA synthesis, but this has not been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and activated peripheral blood mononuclear cells (PBMCs), and in Jurkat T cell leukaemia. PBMCs from men and women (n = 34) were incubated with [1-13C]18:3n-3 with or without Concanavalin A (Con. A). 18:3n-3 conversion was undetectable in unstimulated PBMCs, but up-regulated when stimulated. The main products were 20:3n-3 and 20:4n-3, while 18:4n-3 was undetectable, suggesting initial elongation and Δ8 desaturation. PUFA synthesis was 17.4-fold greater in Jurkat cells than PBMCs. The major products of 18:3n-3 conversion in Jurkat cells were 20:4n-3, 20:5n-3, and 22:5n-3. 13C Enrichment of 18:4n-3 and 20:3n-3 suggests parallel initial elongation and Δ6 desaturation. The FADS2 inhibitor SC26196 reduced PBMC, but not Jurkat cell, proliferation suggesting PUFA synthesis is involved in regulating mitosis in PBMCs. Con. A stimulation increased FADS2, FADS1, ELOVL5 and ELOVL4 mRNA expression in PBMCs. A single transcript corresponding to the major isoform of FADS2, FADS20001, was detected in PBMCs and Jurkat cells. PBMC activation induced hypermethylation of a 470bp region in the FADS2 5′-regulatory sequence. This region was hypomethylated in Jurkat cells compared to quiescent PBMCs. These findings show that PUFA synthesis involving initial elongation and Δ8 desaturation is involved in regulating PBMC proliferation and is regulated via transcription possibly by altered DNA methylation. These processes were dysregulated in Jurkat cells. This has implications for understanding the regulation of mitosis in normal and transformed lymphocytes.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00432/fullperipheral blood mononuclear cellspolyunsaturated fatty acidsdesaturaseelongaseDNA methylationcell proliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charlene M. Sibbons Charlene M. Sibbons Nicola A. Irvine J. Eduardo Pérez-Mojica Philip C. Calder Karen A. Lillycrop Barbara A. Fielding Graham C. Burdge |
spellingShingle |
Charlene M. Sibbons Charlene M. Sibbons Nicola A. Irvine J. Eduardo Pérez-Mojica Philip C. Calder Karen A. Lillycrop Barbara A. Fielding Graham C. Burdge Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells Frontiers in Immunology peripheral blood mononuclear cells polyunsaturated fatty acids desaturase elongase DNA methylation cell proliferation |
author_facet |
Charlene M. Sibbons Charlene M. Sibbons Nicola A. Irvine J. Eduardo Pérez-Mojica Philip C. Calder Karen A. Lillycrop Barbara A. Fielding Graham C. Burdge |
author_sort |
Charlene M. Sibbons |
title |
Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells |
title_short |
Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells |
title_full |
Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells |
title_fullStr |
Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells |
title_full_unstemmed |
Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells |
title_sort |
polyunsaturated fatty acid biosynthesis involving δ8 desaturation and differential dna methylation of fads2 regulates proliferation of human peripheral blood mononuclear cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-03-01 |
description |
Polyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence indicates that immune cell activation involves endogenous PUFA synthesis, but this has not been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and activated peripheral blood mononuclear cells (PBMCs), and in Jurkat T cell leukaemia. PBMCs from men and women (n = 34) were incubated with [1-13C]18:3n-3 with or without Concanavalin A (Con. A). 18:3n-3 conversion was undetectable in unstimulated PBMCs, but up-regulated when stimulated. The main products were 20:3n-3 and 20:4n-3, while 18:4n-3 was undetectable, suggesting initial elongation and Δ8 desaturation. PUFA synthesis was 17.4-fold greater in Jurkat cells than PBMCs. The major products of 18:3n-3 conversion in Jurkat cells were 20:4n-3, 20:5n-3, and 22:5n-3. 13C Enrichment of 18:4n-3 and 20:3n-3 suggests parallel initial elongation and Δ6 desaturation. The FADS2 inhibitor SC26196 reduced PBMC, but not Jurkat cell, proliferation suggesting PUFA synthesis is involved in regulating mitosis in PBMCs. Con. A stimulation increased FADS2, FADS1, ELOVL5 and ELOVL4 mRNA expression in PBMCs. A single transcript corresponding to the major isoform of FADS2, FADS20001, was detected in PBMCs and Jurkat cells. PBMC activation induced hypermethylation of a 470bp region in the FADS2 5′-regulatory sequence. This region was hypomethylated in Jurkat cells compared to quiescent PBMCs. These findings show that PUFA synthesis involving initial elongation and Δ8 desaturation is involved in regulating PBMC proliferation and is regulated via transcription possibly by altered DNA methylation. These processes were dysregulated in Jurkat cells. This has implications for understanding the regulation of mitosis in normal and transformed lymphocytes. |
topic |
peripheral blood mononuclear cells polyunsaturated fatty acids desaturase elongase DNA methylation cell proliferation |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00432/full |
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