Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

Lei Wang, Gudrun Reiterer, Michal J Toborek, Bernhard Hennig

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs) can cause endothelial cell (EC) activation by inducing pro-inflammatory signaling pathways. Our previous studies indicated that linoleic acid (LA, 18:2), a major omega-6 unsaturated fatty acid in the American diet, can potentiate PCB77-mediated inflammatory responses in EC. In addition, omega-3 fatty acids (such as α-linolenic acid, ALA and 18:3) are known for their anti-inflammatory properties. We tested the hypothesis that mechanisms of PCB-induced endothelial cell activation and inflammation can be modified by different ratios of omega-6 to omega-3 fatty acids. EC were pretreated with LA, ALA, or different ratios of these fatty acids, followed by exposure to PCB77. PCB77-induced oxidative stress and activation of the oxidative stress sensitive transcription factor nuclear factor κB (NF-κB) were markedly increased in the presence of LA and diminished by increasing the relative amount of ALA to LA. Similar protective effects by increasing ALA were observed by measuring NF-κB-responsive genes, such as vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2). COX-2 catalyzes the rate limiting step of the biosynthesis of prostaglandin E2 (PGE2). PCB77 exposure also increased PGE2 levels, which were down-regulated with relative increasing amounts of ALA to LA. The present studies suggest that NF-κB is a critical player in the regulation of PCB-induced inflammatory markers as modulated by omega-6 and omega-3 fatty acids.

Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalChemico-Biological Interactions
Volume172
Issue number1
DOIs
StatePublished - Mar 10 2008
Externally publishedYes

Fingerprint

Polychlorinated Biphenyls
Endothelial cells
Omega-3 Fatty Acids
Toxicity
Endothelial Cells
Oxidative stress
Chemical activation
Cyclooxygenase 2
Dinoprostone
Oxidative Stress
Omega-6 Fatty Acids
alpha-Linolenic Acid
Vascular Cell Adhesion Molecule-1
Organic pollutants
Biosynthesis
Linoleic Acid
Nutrition
Unsaturated Fatty Acids
Anti-Inflammatory Agents
Transcription Factors

Keywords

  • Atherosclerosis
  • Inflammation
  • PCB
  • Polyunsaturated fatty acid
  • Vascular endothelial cell

ASJC Scopus subject areas

  • Toxicology

Cite this

Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells. / Wang, Lei; Reiterer, Gudrun; Toborek, Michal J; Hennig, Bernhard.

In: Chemico-Biological Interactions, Vol. 172, No. 1, 10.03.2008, p. 27-38.

Research output: Contribution to journalArticle

@article{e34749c53fde49aa824c9819af3d4c63,
title = "Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells",
abstract = "Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs) can cause endothelial cell (EC) activation by inducing pro-inflammatory signaling pathways. Our previous studies indicated that linoleic acid (LA, 18:2), a major omega-6 unsaturated fatty acid in the American diet, can potentiate PCB77-mediated inflammatory responses in EC. In addition, omega-3 fatty acids (such as α-linolenic acid, ALA and 18:3) are known for their anti-inflammatory properties. We tested the hypothesis that mechanisms of PCB-induced endothelial cell activation and inflammation can be modified by different ratios of omega-6 to omega-3 fatty acids. EC were pretreated with LA, ALA, or different ratios of these fatty acids, followed by exposure to PCB77. PCB77-induced oxidative stress and activation of the oxidative stress sensitive transcription factor nuclear factor κB (NF-κB) were markedly increased in the presence of LA and diminished by increasing the relative amount of ALA to LA. Similar protective effects by increasing ALA were observed by measuring NF-κB-responsive genes, such as vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2). COX-2 catalyzes the rate limiting step of the biosynthesis of prostaglandin E2 (PGE2). PCB77 exposure also increased PGE2 levels, which were down-regulated with relative increasing amounts of ALA to LA. The present studies suggest that NF-κB is a critical player in the regulation of PCB-induced inflammatory markers as modulated by omega-6 and omega-3 fatty acids.",
keywords = "Atherosclerosis, Inflammation, PCB, Polyunsaturated fatty acid, Vascular endothelial cell",
author = "Lei Wang and Gudrun Reiterer and Toborek, {Michal J} and Bernhard Hennig",
year = "2008",
month = "3",
day = "10",
doi = "10.1016/j.cbi.2007.11.003",
language = "English",
volume = "172",
pages = "27--38",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

AU - Wang, Lei

AU - Reiterer, Gudrun

AU - Toborek, Michal J

AU - Hennig, Bernhard

PY - 2008/3/10

Y1 - 2008/3/10

N2 - Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs) can cause endothelial cell (EC) activation by inducing pro-inflammatory signaling pathways. Our previous studies indicated that linoleic acid (LA, 18:2), a major omega-6 unsaturated fatty acid in the American diet, can potentiate PCB77-mediated inflammatory responses in EC. In addition, omega-3 fatty acids (such as α-linolenic acid, ALA and 18:3) are known for their anti-inflammatory properties. We tested the hypothesis that mechanisms of PCB-induced endothelial cell activation and inflammation can be modified by different ratios of omega-6 to omega-3 fatty acids. EC were pretreated with LA, ALA, or different ratios of these fatty acids, followed by exposure to PCB77. PCB77-induced oxidative stress and activation of the oxidative stress sensitive transcription factor nuclear factor κB (NF-κB) were markedly increased in the presence of LA and diminished by increasing the relative amount of ALA to LA. Similar protective effects by increasing ALA were observed by measuring NF-κB-responsive genes, such as vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2). COX-2 catalyzes the rate limiting step of the biosynthesis of prostaglandin E2 (PGE2). PCB77 exposure also increased PGE2 levels, which were down-regulated with relative increasing amounts of ALA to LA. The present studies suggest that NF-κB is a critical player in the regulation of PCB-induced inflammatory markers as modulated by omega-6 and omega-3 fatty acids.

AB - Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs) can cause endothelial cell (EC) activation by inducing pro-inflammatory signaling pathways. Our previous studies indicated that linoleic acid (LA, 18:2), a major omega-6 unsaturated fatty acid in the American diet, can potentiate PCB77-mediated inflammatory responses in EC. In addition, omega-3 fatty acids (such as α-linolenic acid, ALA and 18:3) are known for their anti-inflammatory properties. We tested the hypothesis that mechanisms of PCB-induced endothelial cell activation and inflammation can be modified by different ratios of omega-6 to omega-3 fatty acids. EC were pretreated with LA, ALA, or different ratios of these fatty acids, followed by exposure to PCB77. PCB77-induced oxidative stress and activation of the oxidative stress sensitive transcription factor nuclear factor κB (NF-κB) were markedly increased in the presence of LA and diminished by increasing the relative amount of ALA to LA. Similar protective effects by increasing ALA were observed by measuring NF-κB-responsive genes, such as vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2). COX-2 catalyzes the rate limiting step of the biosynthesis of prostaglandin E2 (PGE2). PCB77 exposure also increased PGE2 levels, which were down-regulated with relative increasing amounts of ALA to LA. The present studies suggest that NF-κB is a critical player in the regulation of PCB-induced inflammatory markers as modulated by omega-6 and omega-3 fatty acids.

KW - Atherosclerosis

KW - Inflammation

KW - PCB

KW - Polyunsaturated fatty acid

KW - Vascular endothelial cell

UR - http://www.scopus.com/inward/record.url?scp=39549111013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39549111013&partnerID=8YFLogxK

U2 - 10.1016/j.cbi.2007.11.003

DO - 10.1016/j.cbi.2007.11.003

M3 - Article

C2 - 18155686

AN - SCOPUS:39549111013

VL - 172

SP - 27

EP - 38

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

IS - 1

ER -