Interleukin-1 beta is significantly upregulated in the decidua of spontaneous and recurrent miscarriage placentas

Löb, Sanja; Amann, Niklas; Kühn, Christina; Schmoeckel, Elisa; Wöckel, Achim; Zehni, Alaleh Zati; Kaltofen, Till; Keckstein, Simon; Mumm, Jan‐Niclas; Meister, Sarah; Kolben, Thomas; Mahner, Sven; Jeschke, Udo; Vilsmaier, Theresa�

doi:10.1016/j.jri.2021.103283

Cited by 26 publications

(12 citation statements)

References 51 publications

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“…If there is an imbalance between Th-1 and Th-2, with elevated levels of Th-1 cytokines, the risk of early pregnancy loss significantly increases. IL-1β can induce an elevation in Th-1 cells, which may be one of the causes of miscarriage induced by IL-1β ( 46 ). In this study, using the MR method, we present compelling evidence supporting the link between pregnancy loss and IL-1β, suggesting that IL-1β may play a potential role in promoting pregnancy loss.…”

Section: Discussionmentioning

confidence: 99%

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology

Huang,

Cai,

Ling

et al. 2024

Front. Endocrinol.

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IntroductionPlacental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method.MethodsAfter obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The “ClusterProfiler” R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes.ResultsWe found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1β (IL-1β) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below −5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2.ConclusionsGROA, IL-1β, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology

Huang,

Cai,

Ling

et al. 2024

Front. Endocrinol.

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“…An increased IL-1β presence in the vaginal washings of women at risk of undergoing a preterm birth has been observed [ 64 ]. Additionally, a significant increase in the expression of IL-1β has been reported in the decidua of spontaneous and recurrent miscarriage placentas [ 65 ]. Here, we reported a significantly higher expression of IL-1β in the tissues of decidua, villi, and fetal membranes in the PTB group when they were compared to those of the term birth group ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

The Expression of IL-1β Correlates with the Expression of Galectin-3 in the Tissue at the Maternal–Fetal Interface during the Term and Preterm Labor

Jović

Milovanović

Jovic

et al. 2022

JCM

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The inflammatory processes that occur at the maternal–fetal interface are considered one of the factors that are responsible for preterm birth. The pro-inflammatory roles of the Gal-3-induced activation of NLRP3 inflammasome and the consecutive production of IL-1β have been described in several acute and chronic inflammatory diseases, but the role of this inflammatory axis in parturition has not been studied. The aim of this study was to analyze the protein expression of Gal-3, NLRP3, and IL-1β in the decidua, villi, and fetal membranes, and to analyze their mutual correlation and correlation with the clinical parameters of inflammation in preterm birth (PTB) and term birth (TB). The study included 40 women that underwent a preterm birth (gestational age of 25.0–36.6) and histological chorioamnionitis (PTB) and control subjects, 22 women that underwent a term birth (gestational age of 37.0–41.6) without histological chorioamnionitis (TB). An analysis of the tissue sections that were stained with anti- Gal-3, -NLRP3, and -IL-1β antibodies was assessed by three independent investigators. The expression levels of Gal-3 and IL-1β were significantly higher (p < 0.001) in the decidua, villi, and fetal membranes in the PTB group when they compared to those of the TB group, while there was no difference in the expression of NLRP3. A further analysis revealed that there was no correlation between the protein expression of NLRP3 and the expression of Gal-3 and IL-1β, but there was a correlation between the expression of Gal-3 and IL-1β in decidua (R = 0.401; p = 0.008), villi (R = 0.301; p = 0.042) and the fetal membranes (R = 0.428; p = 0.002) in both of the groups, PTB and TB. In addition, the expression of Gal-3 and IL-1β in decidua and the fetal membranes was in correlation with the parameters of inflammation in the maternal and fetal blood (C-reactive protein, leukocyte number, and fibrinogen). The strong correlation between the expression of Gal-3 and IL-1β in the placental and fetal tissues during labor indicates that Gal-3 may participate in the regulation of the inflammatory processes in the placenta, leading to increased production of IL-1β, a cytokine that plays the main role in both term and preterm birth.

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“…Recognizing the relationship between maternal Th1/Th2 cytokines and unexplained recurrent spontaneous abortion (URSA) helps in the early diagnosis of URSA as well as treatment monitoring, and IFN-γ/IL-4 in the early diagnosis of URSA reduces the rate of missed diagnoses ( 119 , 120 ). In addition to IL-4, IL-6, IL-1, and IL-12 can be found at altered levels in patients with RSA ( 121 – 123 ) ( Table 1 ).…”

Section: Mmp and Pregnancy-related Diseasesmentioning

confidence: 99%

Insights into the immunomodulatory regulation of matrix metalloproteinase at the maternal-fetal interface during early pregnancy and pregnancy-related diseases

et al. 2023

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Trophoblast immune cell interactions are central events in the immune microenvironment at the maternal-fetal interface. Their abnormalities are potential causes of various pregnancy complications, including pre-eclampsia and recurrent spontaneous abortion. Matrix metalloproteinase (MMP) is highly homologous, zinc(II)-containing metalloproteinase involved in altered uterine hemodynamics, closely associated with uterine vascular remodeling. However, the interactions between MMP and the immune microenvironment remain unclear. Here we discuss the key roles and potential interplay of MMP with the immune microenvironment in the embryo implantation process and pregnancy-related diseases, which may contribute to understanding the establishment and maintenance of normal pregnancy and providing new therapeutic strategies. Recent studies have shown that several tissue inhibitors of metalloproteinases (TIMPs) effectively prevent invasive vascular disease by modulating the activity of MMP. We summarize the main findings of these studies and suggest the possibility of TIMPs as emerging biomarkers and potential therapeutic targets for a range of complications induced by abnormalities in the immune microenvironment at the maternal-fetal interface. MMP and TIMPs are promising targets for developing new immunotherapies to treat pregnancy-related diseases caused by immune imbalance.

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Interleukin-1 beta is significantly upregulated in the decidua of spontaneous and recurrent miscarriage placentas

Cited by 26 publications

References 51 publications

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology

The Expression of IL-1β Correlates with the Expression of Galectin-3 in the Tissue at the Maternal–Fetal Interface during the Term and Preterm Labor

Insights into the immunomodulatory regulation of matrix metalloproteinase at the maternal-fetal interface during early pregnancy and pregnancy-related diseases

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