Proinflammatory properties of coplanar PCBs: In vitro and in vivo evidence

Bernhard Hennig, Purushothaman Meerarani, Rabih Slim, Michal J Toborek, Alan Daugherty, Allen E. Silverstone, Larry W. Robertson

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

So-called coplanar polychlorinated biphenyls (PCBs), as well as other environmental contaminants that are aryl hydrocarbon receptor (AhR) agonists, may compromise the normal functions of vascular endothelial cells by activating oxidative stress-sensitive signaling pathways and subsequent proinflammatory events critical in the pathology of atherosclerosis and cardiovascular disease. To test this hypothesis, porcine endothelial cells were exposed to PCB 153 and to three coplanar PCBs (PCB 77, PCB 126, or PCB 169). In contrast to PCB 153, which is not a ligand for the Ah receptor (AhR), all coplanar PCBs disrupted endothelial barrier function. All coplanar PCBs increased expression of the CYP1A1 gene, oxidative stress (DCF fluorescence), and the DNA-binding activity of nuclear factor κB (NF-κB). PCB-induced oxidative stress was concentration-dependent, with PCB 126 exhibiting a maximal response at the lowest concentration (0.5 μM) tested. The increase in NF-κB-dependent transcriptional activity was confirmed in endothelial cells by a luciferase reporter gene assay. In contrast to PCB 153, coplanar PCBs that are AhR ligands increased endothelial production of interleukin-6. At 3.4 μM, expression of the adhesion molecule VCAM-1 was most sensitive to PCB 77 and 169. We also provide in vivo evidence, suggesting that binding to the AhR is critical for the proinflammatory properties of PCBs. Twenty hours after a single administration of PCB 77, VCAM-1 expression was increased only in wild-type mice, while mice lacking the AhR gene showed no increased staining for VCAM-1. These data provide evidence that coplanar PCBs, agonists for the AhR, and inducers of cytochrome P450 1A1, produce oxidative stress and an inflammatory response in vascular endothelial cells. An intact AhR may be necessary for the observed PCB-induced responses. These findings suggest that activation of the AhR can be an underlying mechanism of atherosclerosis mediated by certain environmental contaminants.

Original languageEnglish
Pages (from-to)174-183
Number of pages10
JournalToxicology and Applied Pharmacology
Volume181
Issue number3
DOIs
StatePublished - Jul 22 2002
Externally publishedYes

Fingerprint

Polychlorinated Biphenyls
Aryl Hydrocarbon Receptors
Oxidative stress
Endothelial cells
Vascular Cell Adhesion Molecule-1
Oxidative Stress
Endothelial Cells
In Vitro Techniques
Genes
Atherosclerosis
Impurities
Ligands
Cytochrome P-450 CYP1A1
Pathology

Keywords

  • Aryl hydrocarbon receptor
  • Atherosclerosis
  • Disease
  • Endothelial cells
  • Environmental contaminants
  • Oxidative stress
  • Polychlorinated biphenyls

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Hennig, B., Meerarani, P., Slim, R., Toborek, M. J., Daugherty, A., Silverstone, A. E., & Robertson, L. W. (2002). Proinflammatory properties of coplanar PCBs: In vitro and in vivo evidence. Toxicology and Applied Pharmacology, 181(3), 174-183. https://doi.org/10.1006/taap.2002.9408

Proinflammatory properties of coplanar PCBs : In vitro and in vivo evidence. / Hennig, Bernhard; Meerarani, Purushothaman; Slim, Rabih; Toborek, Michal J; Daugherty, Alan; Silverstone, Allen E.; Robertson, Larry W.

In: Toxicology and Applied Pharmacology, Vol. 181, No. 3, 22.07.2002, p. 174-183.

Research output: Contribution to journalArticle

Hennig, B, Meerarani, P, Slim, R, Toborek, MJ, Daugherty, A, Silverstone, AE & Robertson, LW 2002, 'Proinflammatory properties of coplanar PCBs: In vitro and in vivo evidence', Toxicology and Applied Pharmacology, vol. 181, no. 3, pp. 174-183. https://doi.org/10.1006/taap.2002.9408
Hennig, Bernhard ; Meerarani, Purushothaman ; Slim, Rabih ; Toborek, Michal J ; Daugherty, Alan ; Silverstone, Allen E. ; Robertson, Larry W. / Proinflammatory properties of coplanar PCBs : In vitro and in vivo evidence. In: Toxicology and Applied Pharmacology. 2002 ; Vol. 181, No. 3. pp. 174-183.
@article{5c4197d5b0924db583f24ef94f5ce265,
title = "Proinflammatory properties of coplanar PCBs: In vitro and in vivo evidence",
abstract = "So-called coplanar polychlorinated biphenyls (PCBs), as well as other environmental contaminants that are aryl hydrocarbon receptor (AhR) agonists, may compromise the normal functions of vascular endothelial cells by activating oxidative stress-sensitive signaling pathways and subsequent proinflammatory events critical in the pathology of atherosclerosis and cardiovascular disease. To test this hypothesis, porcine endothelial cells were exposed to PCB 153 and to three coplanar PCBs (PCB 77, PCB 126, or PCB 169). In contrast to PCB 153, which is not a ligand for the Ah receptor (AhR), all coplanar PCBs disrupted endothelial barrier function. All coplanar PCBs increased expression of the CYP1A1 gene, oxidative stress (DCF fluorescence), and the DNA-binding activity of nuclear factor κB (NF-κB). PCB-induced oxidative stress was concentration-dependent, with PCB 126 exhibiting a maximal response at the lowest concentration (0.5 μM) tested. The increase in NF-κB-dependent transcriptional activity was confirmed in endothelial cells by a luciferase reporter gene assay. In contrast to PCB 153, coplanar PCBs that are AhR ligands increased endothelial production of interleukin-6. At 3.4 μM, expression of the adhesion molecule VCAM-1 was most sensitive to PCB 77 and 169. We also provide in vivo evidence, suggesting that binding to the AhR is critical for the proinflammatory properties of PCBs. Twenty hours after a single administration of PCB 77, VCAM-1 expression was increased only in wild-type mice, while mice lacking the AhR gene showed no increased staining for VCAM-1. These data provide evidence that coplanar PCBs, agonists for the AhR, and inducers of cytochrome P450 1A1, produce oxidative stress and an inflammatory response in vascular endothelial cells. An intact AhR may be necessary for the observed PCB-induced responses. These findings suggest that activation of the AhR can be an underlying mechanism of atherosclerosis mediated by certain environmental contaminants.",
keywords = "Aryl hydrocarbon receptor, Atherosclerosis, Disease, Endothelial cells, Environmental contaminants, Oxidative stress, Polychlorinated biphenyls",
author = "Bernhard Hennig and Purushothaman Meerarani and Rabih Slim and Toborek, {Michal J} and Alan Daugherty and Silverstone, {Allen E.} and Robertson, {Larry W.}",
year = "2002",
month = "7",
day = "22",
doi = "10.1006/taap.2002.9408",
language = "English",
volume = "181",
pages = "174--183",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Proinflammatory properties of coplanar PCBs

T2 - In vitro and in vivo evidence

AU - Hennig, Bernhard

AU - Meerarani, Purushothaman

AU - Slim, Rabih

AU - Toborek, Michal J

AU - Daugherty, Alan

AU - Silverstone, Allen E.

AU - Robertson, Larry W.

PY - 2002/7/22

Y1 - 2002/7/22

N2 - So-called coplanar polychlorinated biphenyls (PCBs), as well as other environmental contaminants that are aryl hydrocarbon receptor (AhR) agonists, may compromise the normal functions of vascular endothelial cells by activating oxidative stress-sensitive signaling pathways and subsequent proinflammatory events critical in the pathology of atherosclerosis and cardiovascular disease. To test this hypothesis, porcine endothelial cells were exposed to PCB 153 and to three coplanar PCBs (PCB 77, PCB 126, or PCB 169). In contrast to PCB 153, which is not a ligand for the Ah receptor (AhR), all coplanar PCBs disrupted endothelial barrier function. All coplanar PCBs increased expression of the CYP1A1 gene, oxidative stress (DCF fluorescence), and the DNA-binding activity of nuclear factor κB (NF-κB). PCB-induced oxidative stress was concentration-dependent, with PCB 126 exhibiting a maximal response at the lowest concentration (0.5 μM) tested. The increase in NF-κB-dependent transcriptional activity was confirmed in endothelial cells by a luciferase reporter gene assay. In contrast to PCB 153, coplanar PCBs that are AhR ligands increased endothelial production of interleukin-6. At 3.4 μM, expression of the adhesion molecule VCAM-1 was most sensitive to PCB 77 and 169. We also provide in vivo evidence, suggesting that binding to the AhR is critical for the proinflammatory properties of PCBs. Twenty hours after a single administration of PCB 77, VCAM-1 expression was increased only in wild-type mice, while mice lacking the AhR gene showed no increased staining for VCAM-1. These data provide evidence that coplanar PCBs, agonists for the AhR, and inducers of cytochrome P450 1A1, produce oxidative stress and an inflammatory response in vascular endothelial cells. An intact AhR may be necessary for the observed PCB-induced responses. These findings suggest that activation of the AhR can be an underlying mechanism of atherosclerosis mediated by certain environmental contaminants.

AB - So-called coplanar polychlorinated biphenyls (PCBs), as well as other environmental contaminants that are aryl hydrocarbon receptor (AhR) agonists, may compromise the normal functions of vascular endothelial cells by activating oxidative stress-sensitive signaling pathways and subsequent proinflammatory events critical in the pathology of atherosclerosis and cardiovascular disease. To test this hypothesis, porcine endothelial cells were exposed to PCB 153 and to three coplanar PCBs (PCB 77, PCB 126, or PCB 169). In contrast to PCB 153, which is not a ligand for the Ah receptor (AhR), all coplanar PCBs disrupted endothelial barrier function. All coplanar PCBs increased expression of the CYP1A1 gene, oxidative stress (DCF fluorescence), and the DNA-binding activity of nuclear factor κB (NF-κB). PCB-induced oxidative stress was concentration-dependent, with PCB 126 exhibiting a maximal response at the lowest concentration (0.5 μM) tested. The increase in NF-κB-dependent transcriptional activity was confirmed in endothelial cells by a luciferase reporter gene assay. In contrast to PCB 153, coplanar PCBs that are AhR ligands increased endothelial production of interleukin-6. At 3.4 μM, expression of the adhesion molecule VCAM-1 was most sensitive to PCB 77 and 169. We also provide in vivo evidence, suggesting that binding to the AhR is critical for the proinflammatory properties of PCBs. Twenty hours after a single administration of PCB 77, VCAM-1 expression was increased only in wild-type mice, while mice lacking the AhR gene showed no increased staining for VCAM-1. These data provide evidence that coplanar PCBs, agonists for the AhR, and inducers of cytochrome P450 1A1, produce oxidative stress and an inflammatory response in vascular endothelial cells. An intact AhR may be necessary for the observed PCB-induced responses. These findings suggest that activation of the AhR can be an underlying mechanism of atherosclerosis mediated by certain environmental contaminants.

KW - Aryl hydrocarbon receptor

KW - Atherosclerosis

KW - Disease

KW - Endothelial cells

KW - Environmental contaminants

KW - Oxidative stress

KW - Polychlorinated biphenyls

UR - http://www.scopus.com/inward/record.url?scp=0036311088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036311088&partnerID=8YFLogxK

U2 - 10.1006/taap.2002.9408

DO - 10.1006/taap.2002.9408

M3 - Article

C2 - 12079426

AN - SCOPUS:0036311088

VL - 181

SP - 174

EP - 183

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 3

ER -