Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction.
Normal pregnancy is the controlled state of inflammation and this systemic inflammatory response is reported to be more intense in preeclampsia. The current study tested the hypothesis that maternal serum stimulates interleukin 6 (IL-6) production from endothelial cells and that nicotine inhibits these effects. Human umbilical vein endothelial cells (HUVECs) were incubated with or without 0.5% serum from healthy pregnant women at term (n = 5) and treated with or without nicotine (10(-9) to 10(-6) mol/L) in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. Interleukin 6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by enzyme-linked immunosorbent assay (ELISA)-based method. Interleukin 6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Nicotine inhibited inflammatory reaction through NF-kB suppression in vitro model of maternal vascular endothelium, and this effect may be one of the explanations for the reduced risk of preeclampsia in smokers.
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