Journal Article

PCB 104-Induced Proinflammatory Reactions in Human Vascular Endothelial Cells: Relationship to Cancer Metastasis and Atherogenesis

Wangsun Choi, Sung Yong Eum, Yong Woo Lee, Bernhard Hennig, Larry W. Robertson and Michal Toborek

in Toxicological Sciences

Volume 75, issue 1, pages 47-56
Published in print September 2003 | ISSN: 1096-6080
Published online September 2003 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfg149
PCB 104-Induced Proinflammatory Reactions in Human Vascular Endothelial Cells: Relationship to Cancer Metastasis and Atherogenesis

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Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that are known to induce carcinogenic and possibly atherogenic events. Recent evidence suggests that selected PCBs may be potent developmental agents of vascular inflammatory responses by inducing cellular oxidative stress and activating redox-responsive transcription factors. Therefore, the aim of this paper is to investigate PCB-induced proinflammatory reactions in human vascular endothelial cells. To determine the proinflammatory effects, cellular oxidative stress and expression of genes encoding for monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules, such as E-selectin and intercellular adhesion molecule-1 (ICAM-1), were assessed in human umbilical vein endothelial cells (HUVEC) exposed to 2,2′,4,6,6′-pentachlorobiphenyl (PCB 104), a representative of ortho-substituted, non-coplanar PCB congeners. PCB 104 increased the oxidative stress in endothelial cells, as determined by the increased 2′,7′-dichlorofluorescein (DCF) and rhodamine 123 fluorescence. In addition, PCB 104 markedly upregulated the expression of MCP-1, E-selectin, and ICAM-1 at both the mRNA and protein levels. These effects were time- and concentration-dependent. The maximum expression of inflammatory genes was observed in endothelial cells exposed to 20 μM of PCB 104 for 1 or 2 h, depending on the specific gene. In addition, PCB 104 elevated the adhesion of THP-1 cells (a human acute monocytic leukemia cell line) to endothelial cell monolayers. These results indicate that PCB 104 is a potent stimulant of inflammatory mediators in human vascular endothelial cells. We hypothesize that these proinflammatory processes may contribute to the development of cancer metastasis and/or atherogenesis in patients exposed to PCBs.

Keywords: PCB; endothelial cells; inflammation; metastasis; atherosclerosis; vascular disease

Journal Article.  6965 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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