Although higher nuclear factor κB (NFκB) expression and activity is observed in preeclamptic placentas, its mechanism of activation is unknown. This is the first study to investigate whether the canonical, non-canonical, or atypical NFκB activation pathways may be responsible for the higher activation of NFκB observed in preeclamptic placentas. The study included 268 cases (130 preeclamptic women and 138 controls). We studied the expression of the genes coding for NFκB activators (NIK, IKKα, IKKβ, and CK2α) and inhibitors (IκBα and IκBβ) using RT-PCR in real time. The RT-PCR results were verified on the protein level using ELISA and Western blot. To determine the efficiency of the pathways, the ratios of activator(s) to one of the inhibitors (IκBα or IκBβ) were calculated for each studied pathway. The preeclamptic placentas demonstrated significantly lower IKKα and CK2α but higher IκBα and IκBβ protein levels. In addition, the calculated activator(s) to inhibitor (IκBα or IκBβ) ratios suggested that all studied pathways might be downregulated in preeclamptic placentas. Our results indicate that preeclamptic placentas may demonstrate mechanisms of NFκB activation other than the canonical, non-canonical, and atypical forms. In these mechanisms, inhibitors of NFκB may play a key role. These observations broaden the existing knowledge regarding the molecular background of preeclampsia development.
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with progressive activity. The RA remission was observed in women during pregnancy, but the mechanism responsible for remission is hypothetical only and concerns mechanisms of immune regulation such as lymphocyte subpopulations and interleukin production. AIMS: The lymphocyte subpopulations and interleukin production in vitro in a group of healthy non-pregnant women, healthy pregnant women and pregnant women suffering from RA may help towards a better understanding of regulation of the immune processes. METHODS: The investigations were performed in trimester III--2 days after delivery and 6 weeks after delivery. Peripheral blood lymphocytes were isolated on Gradisol gradient and analysed immediately or after having been cultured for 72 hours in RPMI medium supplemented with 10% FCS. The cultures were terminated after 72 h, supernatants stored at -72 degrees C for interleukin evaluation. The concentrations of IFN-gamma, IL-2, IL-6, IL-12, TNF-alpha and its soluble receptors R-I, R-II were estimated in non-stimulated and PHA (Sigma, 5 microg/ml) stimulated culture supernatants using ELISA Endogen kits according to the manufacturer's instructions. RESULTS: The general pattern of T cell subpopulation distribution was similar in all analysed groups. Decreased IFN-gamma, IL-12 and increased IL-6 production by lymphocytes after PHA stimulation was found in trimester III in pregnant women with RA as compared to healthy pregnant woman. CONCLUSION: The obtained results suggest that in pregnant women with RA the TH1 cell response predominates, contrary to healthy pregnant women with TH2 type functional response. These phenomena were not observed after delivery.
Background Metalloproteinases (MMPs) play a pivotal role during the process of trophoblast invasion and placentation. The appearance of five functional single-nucleotide polymorphisms (SNP) in the genes of the metalloproteinases most commonly implicated in the implantation process may influence the development of preeclampsia. Methods Blood samples were collected from 86 mothers and 86 children after preeclampsia and 85 mothers and 85 children with uncomplicated pregnancies. The distribution of genotypes for −1607 1G/2G MMP1, −735 C/T MMP2, −1306 C/T MMP2, −1171 5A/6A MMP3, and −1562C/T MMP9 polymorphisms was determined by RFLP-PCR. Results The occurrence of 1G/1G MMP1 or 5A/5A MMP3 genotype in the mother or 1G/1G MMP1 or 5A/6A MMP3 genotype in the child is associated with preeclampsia development. Moreover, simultaneous maternal and fetal 1G/1G homozygosity increases the risk of preeclampsia development 2.39-fold and the set of maternal 5A/5A and fetal 5A/6A MMP3 genotypes by over 4.5 times. No association between the carriage of studied MMP2 or MMP9 polymorphisms and the predisposition to preeclampsia was found. Conclusion The maternal 1G/1G MMP1 and 5A/5A MMP3 and fetal 1G/1G MMP1 and 5A/6A MMP3 gene polymorphisms may be strong genetic markers of preeclampsia, occurring either individually or together.
IntroductionAssessment of leptin concentration in the blood of pregnant women (leptin concentration – Lc) and in their newborns, according to their nutritional status.Material and methodsPregnant women (n = 42) were divided into normal body mass (NBM) and excessive body mass (EBM) groups. Neonates were divided into AGA (eutrophic) and LGA (macrosomic) groups. Leptin concentraction was studied in 4 subgroups: NBM/AGA, NBM/LGA, EBM/AGA, EBM/LGA.ResultsMothers: A significant correlation was found between maternal Lc and body mass index (BMI) (r = 0.75, p < 0.001). Maternal Lc was 3 times higher than neonatal Lc (p < 0.00001). The NBM mothers showed lower Lc compared to EBM mothers (p = 0.000018). Leptin concentration values in NBM/LGA and NBM/AGA mothers were similar (p = 0.6775). Newborns: Correlations were found between Lc and ponderal index (PI) (r = 0.67, p < 0.001), weight (r = 0.43, p = 0.004) and placental weight (r = 0.56, p < 0.001). Girls presented higher Lc than boys (p = 0.0338). In LGA groups, newborns born to EBM mothers presented higher Lc than those born to NBM mothers (p = 0.0013). In both AGA groups, Lc was similar (AGA/EBM vs. AGA/NBM p = 0.1619). The highest Lc and the largest placentas were found in the group of LGA newborns born to EBM mothers.ConclusionsLeptin concentration positively correlates with BMI in pregnant women, with PI and female sex in newborns as well as with placental weight. The nutritional status of fetuses does not affect the Lc of their non-obese mothers. The LGA neonates born to EBM women demonstrate higher Lc than LGA neonates born to NBM mothers, whereas Lc of AGA neonates is similar regardless of the nutritional status of their mothers.
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