Changes of the expression of innate immunity receptors NOD-1, TLR8, ZBP-1, RIG-1 in myometrium during preeclampsia
AbstractIntroduction. Preeclampsia (PE) is characterized by excessive and progressive activation of the immune system against the background of increased levels of pro-inflammatory cytokines and antiangiogenic factors in the placenta as well as in vascular endothelium in pregnant women. At the same time, researchers focus on the pathology of the placenta, while the state of the myometrium in this pathology remains unclear. Pattern recognition receptors (PRRs): Toll-like (TLRs), NOD-like (NLRs), RIG-like (RLRs) and DAI (DNA-binding protein 1, ZBP-1) play an important role in innate immunity and are expressed not only in immune, but also in non-immune cells. It is assumed that some of the clinical manifestations of PE are caused by common underlying inflammatory mechanisms regulated by PRRs.
Aim – to analyze the expression of TLR8, NOD-1, RIG-1 and ZBP-1 in myocytes, endothelium and mesenchymal fibroblast-like cells (FBC) in uterine wall during PE.
Material and methods. The study was performed on myometrial samples obtained during caesarean section (CS) from the anterior wall of the uterus of 22 women of reproductive age (18–43 years), at a period of 27–39 weeks of gestation, of which 12 patients were diagnosed with PE (6 patients had severe PE, 6 – moderate). The group of comparison consisted of 10 women with uncomplicated full-term pregnancy. An immunohistochemical (IHC) study was performed on serial sections of the uterus using polyclonal antibodies to NOD-1, TLR8, ZBP-1 (DLM/DAI), RIG-1.
Results. The study in the patients with uncomplicated pregnancy revealed a uniform expression of all the examined PRRs in smooth muscle cells, vascular endothelium and FBC. In PE we detected a pronounced irregularity in staining of myometrium. In moderate PE, an increase in the expression of ZBP-1 in the FBC and endothelium and NOD-1 in the endothelium was noted relative to the group of comparison. Severe PE, in turn, unlike moderate PE, was characterized by low expression of RIG-1 in the endothelium and FBC, decreased expression of NOD1, and increased expression of TLR8 in the vascular endothelium.
Conclusion. IHC features of innate immunity receptor expression in the myometrium are significantly altered in PE, providing new insights into the pathogenesis of PE.
Keywords:myometrium; preeclampsia; pattern-recognizing receptors; fibroblast-like cells; inflammation
For citation: Nizyaeva N.V., Amiraslanov E.Yu., Artem’eva K.A., Stepanova I.I., Shamarakova M.V. Changes of the expression of innate immunity receptors NOD-1, TLR8, ZBP-1, RIG-1 in myometrium during preeclampsia. Immunologiya. 2023; 44 (5): 607–15. DOI: https://doi.org/10.33029/1816-2134-2023-44-5-607-615 (in Russian)
Funding. The study had no sponsor support.
Conflict of interests. Authors declare no conflict of interests.
Authors’ contribution. Research conception and design – Nizyaeva N.V., Shamarakova M.V.; material collection and processing – Amiraslanov E.Yu., Artem’eva K.A., Stepanova I.I.; statistical processing – Artem’eva K.A.; text writing – Artem’eva K.A., Nizyaeva N.V.; editing – Shamarakova M.V.
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