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Background. To correlate Doppler waveform of the uterine and umbilical vessels to placental nitric oxide synthase (NOS) expression in pregnant women with HELLP (hemolysis, elevated liver enzymes, low platelets count) syndrome. Methods. mRNA expression of inducible NOS (iNOS) and endothelial NOS (eNOS) was assessed, after cesarean section, in placental samples from 10 women affected by HELLP syndrome and 10 controls. Pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries were measured. Results. iNOS expression was significantly lower in placenta from women with HELLP syndrome than controls. When comparing the results with Doppler flow measurements, we found a negative correlation between umbilical pulsatility index and eNOS expression ( r = −0.91) and a positive correlation with iNOS expression ( r = 0.86). Conclusions. The reduced iNOS expression in women with HELLP syndrome may indicate the extreme placental dysfunction that is unable to compensate for the endothelial derang...

To assess placental nitric oxide (NO) metabolism related to changes in the uteroplacental circulation during fetal growth restriction (FGR).The resistance index (RI) from the uterine arteries and pulsatility index (PI) from the umbilical artery were determined by Doppler analysis in 15 patients with FGR and 12 healthy controls, before elective cesarean section. Inducible (iNOS) and endothelial (eNOS) NO synthase expression were measured in placental samples. Immunohistochemistry was performed for iNOS location in the placenta.During FGR, we observed a significant elevation of iNOS when compared with controls. Conversely, eNOS did not differ between the two groups. A negative correlation with eNOS (r = -0.85) and a positive correlation with iNOS (r = 0.91) was found correlating to umbilical PI. The iNOS proteins were reduced in syncytiotrophoblast cells and increased in endothelium in the FGR group compared to the controls.During FGR, placental iNOS expression is significantly increased; this increase possibly represents an adaptive physiological mechanism for overcoming a fetoplacental circulation deficiency.

Green tea has been reported to show anti-inflammatory properties because of its inhibitory effects on the expression of several pro-inflammatory genes. Because the inducible nitricoxide synthase (iNOS) plays an important role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by green tea in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. With the use of electrophoretic mobility shift assays, we found a green tea-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1alpha protein and not from antioxidative effects of the green tea extract. Green tea extract inhibited human iNOS expression in a concentration-dependent manner, quantified in terms of iNOS mRNA, iNOS protein, and nitric oxide production in both cell lines. This inhibitory effect of green tea resulted from transcriptional inhibition as shown in reporter gene experiments. These data suggest that green tea extracts may be promising at least as an auxiliary anti-inflammatory principle in chronic inflammatory diseases.

St. John's wort (SJW) has been described to show anti-inflammatory properties due to its inhibitory effects on the expression of pro-inflammatory genes like cyclooxygenase-2, interleukin-6, and inducible nitric-oxide synthase (iNOS). Since iNOS plays a critical role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by SJW in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. SJW extract concentration dependently inhibited human iNOS expression evaluated by measuring the amounts of iNOS mRNA, iNOS protein, and NO production in both cell lines. This inhibitory effect resulted from transcriptional inhibition as shown in reporter gene experiments. With electrophoretic mobility shift experiments, we found a SJW-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1alpha protein. The diminished STAT-1alpha tyrosine phosphorylation resulted from SJW-mediated reduction of Janus kinase 2 activity. These data suggest that extracts from SJW may be a promising anti-inflammatory principle in chronic inflammatory diseases.

SPECIFIC AIMSEpigallocatechin-3-gallate (EGCG), the main polyphenol component of green tea, exerts inhibitory action on urokinase, metalloproteinase, and inducible nitric oxide synthase (NOS II), accounting for its antitumor and anti-inflammatory action. The aim of the present study was to identify in human cell lines the molecular target of EGCG that modulates the expression of a number of genes involved in inflammatory and neoplastic processes.PRINCIPAL FINDINGS1. EGCG blocks interferon γ (IFN-γ)-elicited activation of signal transducers and activators of transcription 1 (STAT1) by interfering with tyrosine phosphorylation in human MDA MB 231 cell lineTreatment of the estrogen nonresponsive human mammary carcinoma cell line MDA MB 231 with lipopolysaccharide (LPS)/IFN-γ/tumor necrosis factor (TNF)-α/interleukin 1β (IL-1β) (MIX) promptly induced the activation of a nuclear factor, NF-κB, that was not affected by the pretreatment with 20 μM EGCG; 20 μM EGCG did not inhibit the constitutively activated nuc...