PMID- 12805654 OWN - NLM STAT- MEDLINE DCOM- 20040802 LR - 20171116 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 75 IP - 1 DP - 2003 Sep TI - PCB 104-induced proinflammatory reactions in human vascular endothelial cells: relationship to cancer metastasis and atherogenesis. PG - 47-56 AB - 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 microM 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. FAU - Choi, Wangsun AU - Choi W AD - Department of Surgery, University of Kentucky, Lexington, Kentucky 40536, USA. FAU - Eum, Sung Yong AU - Eum SY FAU - Lee, Yong Woo AU - Lee YW FAU - Hennig, Bernhard AU - Hennig B FAU - Robertson, Larry W AU - Robertson LW FAU - Toborek, Michal AU - Toborek M LA - eng GR - P42 ES007380/ES/NIEHS NIH HHS/United States GR - P42 ES 07380/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030612 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Chemokine CCL2) RN - 0 (E-Selectin) RN - 0 (Environmental Pollutants) RN - 0 (Reactive Oxygen Species) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - Z4YYF101N3 (2,2',4,6,6'-pentachlorobiphenyl) SB - IM MH - Cell Adhesion/drug effects MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis/genetics MH - E-Selectin/biosynthesis/genetics MH - Endothelium, Vascular/cytology/*drug effects/metabolism MH - Environmental Pollutants/*toxicity MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Antibody Technique MH - Humans MH - Inflammation/chemically induced/metabolism MH - Intercellular Adhesion Molecule-1/biosynthesis/genetics MH - Oxidative Stress MH - Polychlorinated Biphenyls/*toxicity MH - Reactive Oxygen Species/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Up-Regulation EDAT- 2003/06/14 05:00 MHDA- 2004/08/03 05:00 CRDT- 2003/06/14 05:00 PHST- 2003/06/14 05:00 [pubmed] PHST- 2004/08/03 05:00 [medline] PHST- 2003/06/14 05:00 [entrez] AID - kfg149 [pii] AID - 10.1093/toxsci/kfg149 [doi] PST - ppublish SO - Toxicol Sci. 2003 Sep;75(1):47-56. doi: 10.1093/toxsci/kfg149. Epub 2003 Jun 12.