The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis.

A.M. Knaapen; D.M. Curfs; D.M. Pachen; R.W. Gottschalk; M.P.J. de Winther; M.J. Daemen; F.J. van Schooten

doi:10.1016/j.mrfmmm.2006.12.010

The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis.

A.M. Knaapen^*
, D.M. Curfs
, D.M. Pachen
, R.W. Gottschalk
, M.P.J. de Winther
, M.J. Daemen
, F.J. van Schooten

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) has been implicated in the aetiology of atherosclerosis. Previously we showed that chronic exposure of ApoE-/- mice to the prototype PAH benzo[a]pyrene (B[a]P) causes enhanced progression of atherosclerosis, which was characterised by an increased inflammatory cell content in the atherosclerotic plaques. The aim of the present study was to evaluate the effect of B[a]P on vascular expression of monocyte-chemoattractant protein 1 (MCP-1), which is a crucial molecule promoting the recruitment of monocytes into atherosclerotic lesions. We hypothesised that B[a]P-induced expression of MCP-1 is mediated through aryl hydrocarbon receptor (AhR) activation. Initially we performed in vivo studies showing that acute treatment with B[a]P induces MCP-1 gene expression in aortic tissue of ApoE-/- mice. These observations could be confirmed by in vitro studies with human endothelial cells (RF24 cell line and primary HUVEC), showing a dose- and time-dependent increase in MCP-1 expression upon exposure to B[a]P. This was paralleled by an induction of cytochrome P450 1A1 and 1B1, indicating Ah receptor activation. No increased gene expression (MCP-1, CYP1A1 and 1B1) was found upon incubation with the structural isomer benzo[e]pyrene, which is a weak AhR agonist. Moreover, B[a]P-induced MCP-1 gene and protein expression was inhibited by co-treatment with the AhR antagonist alpha-naphthoflavone. In addition to its effect on basal gene expression, we showed that B[a]P significantly enhanced TNFalpha-induced expression of MCP-1. We were unable to block B[a]P-induced MCP-1 expression by antioxidant treatment. In contrast, we found that addition of N-acetylcysteine or vitamin C enhanced transcription of MCP-1 by B[a]P. In conclusion, our studies revealed potent vascular pro-inflammatory effects of B[a]P, as evidenced by AhR-mediated induction of MCP-1. These observations further contribute to the concept that induction of inflammation is a crucial process in PAH-enhanced atherogenesis. AD - Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), The Netherlands. [email protected]

Original language	English
Pages (from-to)	31-41
Journal	Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis
Volume	621
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mrfmmm.2006.12.010
Publication status	Published - 1 Jan 2007

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10.1016/j.mrfmmm.2006.12.010

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Knaapen, A. M., Curfs, D. M., Pachen, D. M., Gottschalk, R. W., de Winther, M. P. J., Daemen, M. J., & van Schooten, F. J. (2007). The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 621(1-2), 31-41. https://doi.org/10.1016/j.mrfmmm.2006.12.010

@article{92dcf4170b884475995a4e3edd83491e,

title = "The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis.",

abstract = "Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) has been implicated in the aetiology of atherosclerosis. Previously we showed that chronic exposure of ApoE-/- mice to the prototype PAH benzo[a]pyrene (B[a]P) causes enhanced progression of atherosclerosis, which was characterised by an increased inflammatory cell content in the atherosclerotic plaques. The aim of the present study was to evaluate the effect of B[a]P on vascular expression of monocyte-chemoattractant protein 1 (MCP-1), which is a crucial molecule promoting the recruitment of monocytes into atherosclerotic lesions. We hypothesised that B[a]P-induced expression of MCP-1 is mediated through aryl hydrocarbon receptor (AhR) activation. Initially we performed in vivo studies showing that acute treatment with B[a]P induces MCP-1 gene expression in aortic tissue of ApoE-/- mice. These observations could be confirmed by in vitro studies with human endothelial cells (RF24 cell line and primary HUVEC), showing a dose- and time-dependent increase in MCP-1 expression upon exposure to B[a]P. This was paralleled by an induction of cytochrome P450 1A1 and 1B1, indicating Ah receptor activation. No increased gene expression (MCP-1, CYP1A1 and 1B1) was found upon incubation with the structural isomer benzo[e]pyrene, which is a weak AhR agonist. Moreover, B[a]P-induced MCP-1 gene and protein expression was inhibited by co-treatment with the AhR antagonist alpha-naphthoflavone. In addition to its effect on basal gene expression, we showed that B[a]P significantly enhanced TNFalpha-induced expression of MCP-1. We were unable to block B[a]P-induced MCP-1 expression by antioxidant treatment. In contrast, we found that addition of N-acetylcysteine or vitamin C enhanced transcription of MCP-1 by B[a]P. In conclusion, our studies revealed potent vascular pro-inflammatory effects of B[a]P, as evidenced by AhR-mediated induction of MCP-1. These observations further contribute to the concept that induction of inflammation is a crucial process in PAH-enhanced atherogenesis. AD - Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), The Netherlands. [email protected]",

author = "A.M. Knaapen and D.M. Curfs and D.M. Pachen and R.W. Gottschalk and \{de Winther\}, M.P.J. and M.J. Daemen and \{van Schooten\}, F.J.",

year = "2007",

month = jan,

day = "1",

doi = "10.1016/j.mrfmmm.2006.12.010",

language = "English",

volume = "621",

pages = "31--41",

journal = "Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis",

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Knaapen, AM, Curfs, DM, Pachen, DM, Gottschalk, RW, de Winther, MPJ, Daemen, MJ & van Schooten, FJ 2007, 'The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis.', Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, vol. 621, no. 1-2, pp. 31-41. https://doi.org/10.1016/j.mrfmmm.2006.12.010

The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis. / Knaapen, A.M.; Curfs, D.M.; Pachen, D.M. et al.
In: Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 621, No. 1-2, 01.01.2007, p. 31-41.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis.

AU - Knaapen, A.M.

AU - Curfs, D.M.

AU - Pachen, D.M.

AU - Gottschalk, R.W.

AU - de Winther, M.P.J.

AU - Daemen, M.J.

AU - van Schooten, F.J.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) has been implicated in the aetiology of atherosclerosis. Previously we showed that chronic exposure of ApoE-/- mice to the prototype PAH benzo[a]pyrene (B[a]P) causes enhanced progression of atherosclerosis, which was characterised by an increased inflammatory cell content in the atherosclerotic plaques. The aim of the present study was to evaluate the effect of B[a]P on vascular expression of monocyte-chemoattractant protein 1 (MCP-1), which is a crucial molecule promoting the recruitment of monocytes into atherosclerotic lesions. We hypothesised that B[a]P-induced expression of MCP-1 is mediated through aryl hydrocarbon receptor (AhR) activation. Initially we performed in vivo studies showing that acute treatment with B[a]P induces MCP-1 gene expression in aortic tissue of ApoE-/- mice. These observations could be confirmed by in vitro studies with human endothelial cells (RF24 cell line and primary HUVEC), showing a dose- and time-dependent increase in MCP-1 expression upon exposure to B[a]P. This was paralleled by an induction of cytochrome P450 1A1 and 1B1, indicating Ah receptor activation. No increased gene expression (MCP-1, CYP1A1 and 1B1) was found upon incubation with the structural isomer benzo[e]pyrene, which is a weak AhR agonist. Moreover, B[a]P-induced MCP-1 gene and protein expression was inhibited by co-treatment with the AhR antagonist alpha-naphthoflavone. In addition to its effect on basal gene expression, we showed that B[a]P significantly enhanced TNFalpha-induced expression of MCP-1. We were unable to block B[a]P-induced MCP-1 expression by antioxidant treatment. In contrast, we found that addition of N-acetylcysteine or vitamin C enhanced transcription of MCP-1 by B[a]P. In conclusion, our studies revealed potent vascular pro-inflammatory effects of B[a]P, as evidenced by AhR-mediated induction of MCP-1. These observations further contribute to the concept that induction of inflammation is a crucial process in PAH-enhanced atherogenesis. AD - Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), The Netherlands. [email protected]

AB - Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) has been implicated in the aetiology of atherosclerosis. Previously we showed that chronic exposure of ApoE-/- mice to the prototype PAH benzo[a]pyrene (B[a]P) causes enhanced progression of atherosclerosis, which was characterised by an increased inflammatory cell content in the atherosclerotic plaques. The aim of the present study was to evaluate the effect of B[a]P on vascular expression of monocyte-chemoattractant protein 1 (MCP-1), which is a crucial molecule promoting the recruitment of monocytes into atherosclerotic lesions. We hypothesised that B[a]P-induced expression of MCP-1 is mediated through aryl hydrocarbon receptor (AhR) activation. Initially we performed in vivo studies showing that acute treatment with B[a]P induces MCP-1 gene expression in aortic tissue of ApoE-/- mice. These observations could be confirmed by in vitro studies with human endothelial cells (RF24 cell line and primary HUVEC), showing a dose- and time-dependent increase in MCP-1 expression upon exposure to B[a]P. This was paralleled by an induction of cytochrome P450 1A1 and 1B1, indicating Ah receptor activation. No increased gene expression (MCP-1, CYP1A1 and 1B1) was found upon incubation with the structural isomer benzo[e]pyrene, which is a weak AhR agonist. Moreover, B[a]P-induced MCP-1 gene and protein expression was inhibited by co-treatment with the AhR antagonist alpha-naphthoflavone. In addition to its effect on basal gene expression, we showed that B[a]P significantly enhanced TNFalpha-induced expression of MCP-1. We were unable to block B[a]P-induced MCP-1 expression by antioxidant treatment. In contrast, we found that addition of N-acetylcysteine or vitamin C enhanced transcription of MCP-1 by B[a]P. In conclusion, our studies revealed potent vascular pro-inflammatory effects of B[a]P, as evidenced by AhR-mediated induction of MCP-1. These observations further contribute to the concept that induction of inflammation is a crucial process in PAH-enhanced atherogenesis. AD - Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), The Netherlands. [email protected]

U2 - 10.1016/j.mrfmmm.2006.12.010

DO - 10.1016/j.mrfmmm.2006.12.010

M3 - Article

C2 - 17376491

SN - 0027-5107

VL - 621

SP - 31

EP - 41

JO - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis

JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis

IS - 1-2

ER -

The environmental carcinogen benzo[a]pyrene induces expression of monocyte-chemoattractant protein-1 in vascular tissue: a possible role in atherogenesis.

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