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Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-κB, and AP-1

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Abstract

Investigation into the etiology of atherosclerosis has identified cigarette smoking as a major risk factor. Although it has been established that cellular adhesion molecule expression on endothelial cells is stimulated by nicotine, the mechanism by which this occurs is not clear. The aim of this study was to determine the effect of nicotine on the expression of the adhesion molecules, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 inendothelial cells and to determine the involvement of imporcule tank known intermediaries, protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and the transcription factors NF-κB and AP-1. Human umbilical vein endothelial cells (HUVEC) were exposed to 10−8 M nicotine for up to 24 h. Expression of ICAM-1 and VCAM-1 and phosphorylation of p38 were examined by immunoblot. Electrophoretic mobility shift assay was performed to determine NF-κB and AP-1 activation. We observed that nicotine increased the expression of ICAM-1 and VCAM-1 with a peak at 6h.p38 MAPK was activated after 5 min exposure to 10−8 mol/L nicotine and returned to baseline levels by 30 min. Exposure of HUVEC to nicotine resulted in a 4.1-fold increase of PKC activity at 5 min, which subsequently returned to control levels by 15 min. Nicotine (10−8 mol/L) also increased NF-κB and AP-1 activity. Inhibitors of p38 MAPK, PKC, and NF-κB suppressed nicotine-stimulated expression of ICAM-1 and VCAM-1. Our results indicate that nicotine enhances the expression of ICAM-1 and VCAM-1 on the endothelial cell surface via a second messenger pathway which involves PKC and p38 MAPK-mediated activation of NF-κB and AP-1, resulting in increased expression of these cellular adhesion molecules.

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Ueno, H., Pradhan, S., Schlessel, D. et al. Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-κB, and AP-1. Cardiovasc Toxicol 6, 39–50 (2006). https://doi.org/10.1385/CT:6:1:39

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  • DOI: https://doi.org/10.1385/CT:6:1:39

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