Активність Р65-субодиниці ядерного чинника NF-KB та співвідношення Т-хелперів І та ІІ типу у вагітних із плацентарними порушеннями й передчасною пологовою діяльністю

I.B. Ventskivska; V.I. Kupchik

doi:10.18370/2309-4117.2023.67.79-83

Authors

I.B. Ventskivska O.O. Bogomolets National Medical University, Kyiv, Ukraine https://orcid.org/0000-0002-7685-5289
V.I. Kupchik O.O. Bogomolets National Medical University, Kyiv , Ukraine https://orcid.org/0000-0002-4394-260X

DOI:

https://doi.org/10.18370/2309-4117.2023.67.79-83

Keywords:

NF-kB p65-subunit, T-helpers type 1, T-helpers type 2, premature birth, placental dysfunction, preterm premature rupture of membranes

Abstract

Objectives: to study the levels of the total, phosphorylated p65-subunit of the nuclear factor NF-kB, activity of p65 and the relation with the level and ratio of T-helpers type I and II in pregnant women with placental dysfunction and different clinical types of the course of preterm labor (with preterm premature rupture of membranes (pPROM) and without it).
Materials and methods. The case-control study included 60 pregnant women: 40 women with placental disorders and spontaneous premature labor in the period of 24–34 weeks (group I – 20 women with premature labor and timely discharge of amniotic fluid, group II – 20 women with pPROM) and 20 women of the control group (CG) with normal timely delivery in the head position of a fetus without complications.
The value of the total NF-kB p65 subunit and its phosphorylated fraction was determined in all women using ELISA in placenta lysates. On this basis the p65 subunit activity was calculated; number of T-helper I (Th1) and T-helper II (Th2) was determined using flow cytometry in a whole blood sample, with afterward calculation of the Th1/Th2 ratio.
Results. Elevated levels of total p65 and its phosphorylated fraction were found in women with placental dysfunction (p < 0.01 in groups I and II compared with CG), as well as the activity p65 (p < 0.01 in group I, p = 0.04 in group II compared with CG). The difference in the Th1 value and the Th1/Th2 ratio was significantly higher in both groups (p < 0.01 in group I, p = 0.03 in group II for Th1; p < 0.01 in both groups for Th1/Th2), the number of Th2 differed significantly only in group I (p < 0.01 compared with CG). A strong positive correlation between p65 activity and Th1/Th2 was also established (r = 0.8).
Conclusions. Obtained data indicates the increased NF-kB p65-subunit activity in women with placental disorders and spontaneous premature labor without pPROM, which is impact on the increase of the Th1/Th2 ratio due to the Th1 increase. This mechanism might be considered to be the leading cause of the premature birth in this group of pregnant women. However, for women with the preterm labor activity with pPROM, the difference with GC has a lower level of significance, which may indicate the existence of another leading mechanism for the initiation of premature labor in this group.

Author Biographies

I.B. Ventskivska, O.O. Bogomolets National Medical University, Kyiv

MD, professor, Obstetrics and Gynecology Department No. 1

V.I. Kupchik, O.O. Bogomolets National Medical University, Kyiv

Graduate student, Department of Obstetrics and Gynecology No. 1

References

Wardinger, J.E., Ambati, S. Placental Insufficiency. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
Leush, S.S., Zagorodnyaya, A.S., Vitovsky, Y.M., Protsik, M.V. “Fetal-maternal gas transport in preterm birth.” Reproductive health. Eastern Europe 11.6 (2021): 722–9.
Malhotra, A., Allison, B.J., Castillo-Melendez, M., et al. “Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact.” Front Endocrinol (Lausanne) 10 (2019): 55.
Fantasia, I., Bussolaro, S., Stampalija, T., Rolnik, D.L. “The role of melatonin in pregnancies complicated by placental insufficiency: A systematic review.” Eur J Obstet Gynecol Reprod Biol 278 (2022): 22–8.
Frolova, T.V., Lazurenko, V.V., Pasiyeshvili, N.M., et al. “Placental dysfunction: health status, nutritional status and mineral profile of a mother-child pair.” Wiad Lek 73.1 (2020): 95–8.
Lien, Y.C., Zhang, Z., Cheng, Y., et al. “Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth.” Int J Mol Sci 22.15 (2020): 7899.
Armengaud, J.B., Yzydorczyk, C., Siddeek, B., et al. “Intrauterine growth restriction: Clinical consequences on health and disease at adulthood.” Reprod Toxicol 99 (2021): 168–76.
Darby, J.R.T., Varcoe, T.J., Orgeig, S., Morrison, J.L. “Cardiorespiratory consequences of intrauterine growth restriction: Influence of timing, severity and duration of hypoxaemia.” Theriogenology 150 (2020): 84–95.
Green, E.S., Arck, P.C. “Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus.” Semin Immunopathol 42.4 (2020): 413–29.
Gomez-Lopez, N., Galaz, J., Miller, D. “The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal-fetal homeostasis.” Reproduction 164.2 (2022): R11–R45.
Muñoz-Pérez, V.M., Ortiz, M.I., Cariño-Cortés, R., et al. “Preterm Birth, Inflammation and Infection: New Alternative Strategies for their Prevention.” Curr Pharm Biotechnol 20.5 (2019): 354–65.
Bila, V., Zahorodnia, O., Tsapenko, T.,Tymoschuk, K. “Glucose Concentration in Amniotic Fluid as a Marker of Amniotic Membrane Inflammation in Premature Rupture in Preterm and Term Pregnancies.” Reproductive health. Eastern Europe 11.6 (2021): 708–16.
Ventskivska, I.B., Zagorodnya, O.S. “Inflammation as a factor of the hourly sloping activity.” World Med Biol 4.78 (2021): 22–6.
Kuroda, K., Nakagawa, K., Horikawa, T. “Increasing number of implantation failures and pregnancy losses associated with elevated Th1/Th2 cell ratio.” Am J Reprod Immunol 86.3 (2021): e13429.
Esparvarinha, M., Madadi, S., Aslanian-Kalkhoran, L. “Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints.” Cell Biol Int (2022). DOI: 10.1002/cbin.11955
Ariyakumar, G., Morris, J.M., McKelvey, K.J., et al. “NF-kB regulation in maternal immunity during normal and IUGR pregnancies.” Sci Rep 11.1 (2021): 20971.
Bila, V.V. “The choice of method of delivery in preterm birth in terms of 24–28 weeks. Experience of the Perinatal Center.” Reproductive health. Eastern Europe 8.4 (2018): 471–8.
Wang, W., Sung, N., Gilman-Sachs, A., Kwak-Kim, J. “T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells.” Front Immunol 11 (2020): 20–5.
Arefieva, A., Nikolaeva, M., Stepanova, E. “Association of CD200 expression in paternal lymphocytes with female Th1/Th2 balance and pregnancy establishment at immunotherapy of recurrent spontaneous abortion.” Am J Reprod Immunol 85.3 (2021): e13355.
Li, Y.X., Long, D.L., Liu, J., Qiu, D. “Gestational diabetes mellitus in women increased the risk of neonatal infection via inflammation and autophagy in the placenta.” Medicine 99.40 (2020): e22152.
Ventskovskaya, I.B., Kupchik, V.I. “New molecular mechanisms of placental dysfunction.” Reproductive health. Eastern Europe 11.6 (2021): 730–9.
Le, Y., Wang, Y., Zhou, L. “Cigarette smoke-induced HMGB1 translocation and release contribute to migration and NF-kB activation through inducing autophagy in lung macrophages.” J Cell Mol Med 24.2 (2020): 1319–31.
Song, H., Zhao, C., Yu, Z. “UAF1 deubiquitinase complexes facilitate NLRP3 inflammasome activation by promoting NLRP3 expression.” Nat Commun 11.1 (2020): 6042.
Yu, G., Yu, H., Yang, Q. “Vibrio harveyi infections induce production of proinflammatory cytokines in murine peritoneal macrophages via activation of p38 MAPK and NF-kB pathways, but reversed by PI3K/AKT pathways.” Dev Comp Immunol 127 (2022): 104292.
Pernaa, N., Keskitalo, S., Chowdhury, I. “Heterozygous premature termination in zinc-finger domain of Krüppel-like factor 2 gene associates with dysregulated immunity.” Front Immunol 13 (2022): 819929.