Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth

Ran, Yuxin; Huang, Dongni; Mei, Youwen; Liu, Zheng; Zhou, Yibei; He, Jie; Zhang, Hanwen; Yin, Ning; Qi, Hongbo

doi:10.1080/21655979.2021.1945894

Cited by 7 publications

(4 citation statements)

References 105 publications

(104 reference statements)

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“…This hypothesis is also reinforced by the increased levels of Ifn-γ , typically linked with a pro-inflammatory state during pregnancy complications [ 41 ]. Il27 , correlated with an immune–inflammatory imbalance in the pre-term [ 42 ], showed increased expression in Hmox1 −/− uteruses. Similarly, the upregulation of Il11 , was previously associated with inflammation and pre-eclampsia features in mice [ 43 ] and Il1b , linked to idiopathic recurrent implantation failure [ 44 ], indicated a pro-inflammatory milieu.…”

Section: Discussionmentioning

confidence: 99%

Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus

Zenclussen,

Ulrich,

Bauer

et al. 2024

Cells

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The enzyme heme oxygenase-1 (HO-1) is pivotal in reproductive processes, particularly in placental and vascular development. This study investigated the role of HO-1 and its byproduct, carbon monoxide (CO), in trophoblastic spheroid implantation. In order to deepen our understanding of the role of HO-1 during implantation, we conducted in vivo experiments on virgin and pregnant mice, aiming to unravel the cellular and molecular mechanisms. Using siRNA, HO-1 was knocked down in JEG-3 and BeWo cells and trophoblastic spheroids were generated with or without CO treatment. Adhesion assays were performed after transferring the spheroids to RL-95 endometrial epithelial cell layers. Additionally, angiogenesis, stress, and toxicity RT2-Profiler™ PCR SuperArray and PCR analyses were performed in uterine murine samples. HO-1 knockdown by siRNA impeded implantation in the 3D culture model, but this effect could be reversed by CO. Uteruses from virgin Hmox1−/− females exhibited altered expression of angiogenesis and stress markers. Furthermore, there was a distinct expression pattern of cytokines and chemokines in uteruses from gestation day 14 in Hmox1−/− females compared to Hmox1+/+ females. This study strongly supports the essential role of HO-1 during implantation. Moreover, CO appears to have the potential to compensate for the lack of HO-1 during the spheroid attachment process. The absence of HO-1 results in dysregulation of angiogenesis and stress-related genes in the uterus, possibly contributing to implantation failure.

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Section: Discussionmentioning

confidence: 99%

Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus

Zenclussen,

Ulrich,

Bauer

et al. 2024

Cells

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“…Ran and his colleagues have reported a strong association between the preterm birth and the high levels of IL-27 in peripheral blood as well as the chorion of pregnant women which reflects systemic changes in both mother and fetus [32]. On the other hand, in healthy neonates, He and his colleagues have reported lack of any significant elevation of IL-27 in absence of infection through measuring its level in umbilical cord blood obtained from 33 healthy neonates without any risk of infection.…”

Section: Discussionmentioning

confidence: 99%

Performance of interleukin-27 cord blood level as a biomarker predicating early onset neonatal sepsis

Sultan,

Seleim,

Elnagar

2023

Microbes and Infectious Diseases

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Background: This study designed to evaluate the level of IL-27 in umbilical cord blood and the possibility of its use as a predictor for diagnosis of Early Onset Neonatal Sepsis (EONS). Methods: This observational analytic study was conducted by enrolling newborn infants born to pregnant women with antenatal risk factors for sepsis. The infection group that included both suspected and confirmed EONS occurred ≤72 hours after delivery compared to non-infection group. Blood samples were collected from the umbilical artery after cord clamping for biomarkers detection and after 24 hours from venous blood. The concentrations of IL-27 and procalcitonin (PCT) were measured by sandwich ELISA assay. Results: A total of 124 neonates were enrolled, 48 (38.7%) neonates were identified in infection group either suspected or confirmed EONS. A significantly higher levels of IL-27 was found in cord blood of babies in the infection group (p<0.01). At 24h after birth, the IL-27 continued to show significantly higher levels in infection group (p<0.01) compared to non-infection group. The IL-27 showed an increased risk of EONS with an odds ratio of 9.13 and p<0.01. The IL-27 through ROC curve analysis showed a better performance in distinguishing neonates with true infection from neonates without infection. A combined performance of IL-27 with PCT in the cord blood and at 24 hours of life showed greater prediction of EONS with p <0.01 for each. Conclusion: The IL-27 level in the blood of the umbilical cord may offer a significant predictive tool for EONS either alone or more significantly in combination with PCT.

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“…Previous data showed that IL-27 could release various inflammatory mediators such as IL-6, IFN-g, TNF-a, IL-1b, MCP-1, MMP9 and CXCL10 mainly via the ERK and JNK signaling pathways (24,25). Therefore, we investigated the inflammatory imbalance mediated by IL-27 in WISH and HMSMC cells.…”

Section: Il-27 Mediated Inflammation Imbalance Via the Erk Signaling Pathwaymentioning

confidence: 96%

IL-27 Mediates Pro-Inflammatory Effects via the ERK Signaling Pathway During Preterm Labor

et al. 2021

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Preterm labor (PTL) is a multifactorial syndrome that results in birth prior to 37 weeks of gestation. However, the specific molecular mechanisms underlying this condition have yet to be elucidated. Previous research demonstrated that the abnormal expression of IL-27, and its receptors, played a role in the pathophysiology of preterm labor. In the present study, we established a Lipopolysaccharide (LPS)-stimulated, infection-induced, preterm mouse model based on wild-type C57BL/6 mice and WSX-1-/-C57BL/6 mice. WSX-1 knockdown led to a significant delay in birth by 11.32 ± 2.157h. In addition, compared with wild-type C57B/6 mice, the expression levels of IFN-γ, IL-1β, IL-6, TNF-α, and CXCL10, in the fetal membrane and myometrium of WSX-1-/-mice were significantly lower, particularly in the myometrium. We also confirmed similar pro-inflammatory effects arising from IL-27 in human amniotic cell line (WISH) and human myometrial smooth muscle cell line (HMSMC). Once stimulated by LPS, the pro-inflammatory action exhibited a synergistic effect and appeared to be time-dependent. Finally, we demonstrated that LY3214996, an inhibitor of the ERK pathway, significantly inhibited the pro-inflammatory effect mediated by IL-27. Overall, our data confirmed that the inflammatory effect mediated by the IL-27/IFN-r/ERK axis is involved in preterm labor. Our findings, therefore, provide an enhancement in our etiological understanding of the mechanisms underlying PTL.

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Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth

Cited by 7 publications

References 105 publications

Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus

Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus

Performance of interleukin-27 cord blood level as a biomarker predicating early onset neonatal sepsis

IL-27 Mediates Pro-Inflammatory Effects via the ERK Signaling Pathway During Preterm Labor

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