IL-33 and Soluble ST2 Are Associated With Recurrent Spontaneous Abortion in Early Pregnancy

Zhao, Liang; Fu, Jianhua; Ding, Feng; Liu, Juan; Li, Lin; Song, Qi; Fu, Ying‐Hui

doi:10.3389/fphys.2021.789829

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…IL-33, is pivotal in regulating angiogenesis and inflammatory immune responses. Recent studies indicate considerably greater serum concentrations of IL-33 ( P < 0.05) and its receptor ST-2 ( P < 0.01) in patients with RPL compared to healthy controls [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

Han,

Wu,

Bian

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

Han,

Wu,

Bian

et al. 2024

Heliyon

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“…Previous studies have demonstrated that IL-33 plays an essential role in several pregnancy-related diseases, including endometriosis, recurrent pregnancy loss and preeclampsia, etc. (Chen H. et al 2018 ; Fock et al 2013 ; Granne et al 2011 ; Miller J. E. et al 2017 ; Salker et al 2012 ; Zhao et al 2021 ). Unlike most of other cytokines, IL-33 can function either as a secreted cytokine or as an intracellular nuclear factor regulating gene expression (Bertheloot et al 2017 ; Cayrol et al 2018 ; 2022 ).…”

Section: Discussionmentioning

confidence: 99%

IL-33/ST2 axis of human amnion fibroblasts participates in inflammatory reactions at parturition

Lei

Zhang

Lin

et al. 2023

Mol Med

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Background Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in inflammation via ST2 (suppression of tumorigenicity 2) receptor as an inflammatory cytokine. However, it remains unknown whether IL-33/ST2 axis exists in human fetal membranes to promote inflammatory reactions in parturition. Methods The presence of IL-33 and ST2 and their changes at parturition were examined with transcriptomic sequencing, quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry in human amnion obtained from term and preterm birth with or without labor. Cultured primary human amnion fibroblasts were utilized to investigate the regulation and the role of IL-33/ST2 axis in the inflammation reactions. A mouse model was used to further study the role of IL-33 in parturition. Results Although IL-33 and ST2 expression were detected in both epithelial and fibroblast cells of human amnion, they are more abundant in amnion fibroblasts. Their abundance increased significantly in the amnion at both term and preterm birth with labor. Lipopolysaccharide, serum amyloid A1 and IL-1β, the inflammatory mediators pertinent to labor onset, could all induce IL-33 expression through NF-κB activation in human amnion fibroblasts. In turn, via ST2 receptor, IL-33 induced the production of IL-1β, IL-6 and PGE2 in human amnion fibroblasts via the MAPKs-NF-κB pathway. Moreover, IL-33 administration induced preterm birth in mice. Conclusion IL-33/ST2 axis is present in human amnion fibroblasts, which is activated in both term and preterm labor. Activation of this axis leads to increased production of inflammatory factors pertinent to parturition, and results in preterm birth. Targeting the IL-33/ST2 axis may have potential value in the treatment of preterm birth.

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“…For example, compared with Cluster-2, Cluster-1 was significantly more enriched in the positive regulation of type 2 immune responses and positive regulation of IL-4 production. Successful pregnancy is closely associated with transition from type 1 to type 2 immune responses (Zhao et al, 2021) and IL-4 cytokine is a signature of type 2 immunity (Gause et al, 2020). Furthermore, GSEA showed that the FoxO signaling pathway was activated in Cluster-1, while the cell cycle and Wnt pathways were inhibited.…”

Section: Discussionmentioning

confidence: 99%

Molecular subtype identification and predictive power of N6-methyladenosine regulator in unexplained recurrent pregnancy loss

et al. 2022

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The etiology of recurrent pregnancy loss (RPL) is complicated and effective clinical preventive measures are lacking. Identifying biomarkers for RPL has been challenging, and to date, little is known about the role of N6-methyladenosine (m6A) regulators in RPL. Expression data for m6A regulators in 29 patients with RPL and 29 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database. To establish a diagnostic model for unexplained RPL, differential gene expression analysis was conducting for 36 m6A regulators using least absolute shrinkage and selection operator (LASSO) regression. Unsupervised cluster analysis was conducted on hub genes, and probable mechanisms were explored using gene set enrichment analysis (GSEA) and gene ontology (GO) analysis. Correlations between m6A-related differentially expressed genes and immune infiltration were analyzed using single-sample GSEA. A total of 18 m6A regulators showed significant differences in expression in RPL: 10 were upregulated and eight were downregulated. Fifteen m6A regulators were integrated and used to construct a diagnostic model for RPL that had good predictive efficiency and robustness in differentiating RPL from control samples, with an overall area under the curve (AUC) value of 0.994. Crosstalk was identified between 10 hub genes, miRNAs, and transcription factors (TFs). For example, YTHDF2 was targeted by mir-1-3p and interacted with embryonic development-related TFs such as FOXA1 and GATA2. YTHDF2 was also positively correlated with METTL14 (r = 0.5983, p < 0.001). Two RPL subtypes (Cluster-1 and Cluster-2) with distinct hub gene signatures were identified. GSEA and GO analysis revealed that the differentially expressed genes were mainly associated with immune processes and cell cycle signaling pathway (normalized enrichment score, NES = -1.626, p < 0.001). Immune infiltration was significantly higher in Cluster-1 than in Cluster-2 (p < 0.01). In conclusion, we demonstrated that m6A modification plays a critical role in RPL. We also developed and validated a diagnostic model for RPL prediction based on m6A regulators. Finally, we identified two distinct RPL subtypes with different biological processes and immune statuses.

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IL-33 and Soluble ST2 Are Associated With Recurrent Spontaneous Abortion in Early Pregnancy

Cited by 10 publications

References 32 publications

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

IL-33/ST2 axis of human amnion fibroblasts participates in inflammatory reactions at parturition

Molecular subtype identification and predictive power of N6-methyladenosine regulator in unexplained recurrent pregnancy loss

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