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The Role of IL-27 in the Systemic Inflammatory Response That Accompanies Preterm Labour

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Abstract

This study aimed to investigate whether interleukin-27 (IL-27) activates maternal peripheral blood mononuclear cells (PBMCs) and induces inflammatory responses in amniotic epithelial cells in preterm labour (PL). The expression of IL-27p28, EBI3 and IL-27Rα was compared in maternal PBMCs of the PL, term labour (TL) and term not in labour (TNL) groups. The relationship between IL-27 and molecules associated with PBMC activation was investigated using bioinformatic and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. We investigated the inflammatory effects of IL-27 in PBMCs and its underlying mechanisms in vitro. In addition, we treated amniotic epithelial cells (WISH cells) with a PBMC-conditioned medium to identify the inflammatory effects of IL-27-treated PBMCs in amniotic epithelial cells. The expression of IL-27p28 and IL-27Rα in PBMCs of the PL group was higher than that in the TL/TNL groups. Bioinformatic analysis revealed that IL-27 was positively correlated with IFNG, IL6, IL1β, CXCL10 and ICAM1 in the whole blood samples of pregnant women in the PL group, which was confirmed using qRT-PCR. Furthermore, rhIL-27 promoted the expression of Th1 cell-related molecules (T-bet, IFN-γ and ICAM-1) and proinflammatory cytokines (IL-6 and IL-1β) in PBMCs in vitro, which was partially mediated by the JAK2/STAT1 pathway. In addition, it enhanced the expression of IL-27p28, EBI3 and IL-27Rα in PBMCs. Moreover, the expression of IL-6, IL-1β and TNF-α in WISH cells was significantly increased by the conditional medium derived from IL-27-treated PBMCs. IL-27 upregulated the expression of Th1 cell-related molecules and proinflammatory cytokines in PBMCs partially mediated by the JAK2/STAT1 pathway. Inflammatory responses were induced in WISH cells by a conditional medium derived from IL-27-treated PBMCs. Therefore, IL-27 may contribute to PL by promoting inflammation in maternal PBMCs and amniotic epithelial cells.

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Abbreviations

IL-27:

Interleukin-27

PBMCs:

Peripheral blood mononuclear cells

PL:

Preterm labour

TL:

Term labour

TNL:

Term not in labour

PNL:

Preterm not in labour

Th:

T helper

Treg:

T regulatory

IL-27R:

IL-27 receptor

JAK:

Janus kinase

STAT:

Signal transducer and activator of transcription

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

IL-27R:

IL-27 receptor

PBS:

Phosphate-buffered saline

WISH:

Wistar Institute Susan Hayflick

CCK8:

Cell Counting Kit 8

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Funding

This study was funded by the National Natural Science Foundation of China for Youth (81801483) and the National Key R&D Program of China (No. 2016YFC1000407).

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Authors and Affiliations

  1. International Collaborative Jointed Laboratory of Maternal and Fetal Medicine, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China

    Youwen Mei, Yuxin Ran, Zheng Liu, Yunqian Zhou, Jie He, Nanlin Yin & Hongbo QI

  2. State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China

    Youwen Mei, Yuxin Ran, Zheng Liu, Yunqian Zhou, Jie He, Nanlin Yin & Hongbo QI

  3. Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Youwen Mei, Yuxin Ran, Zheng Liu, Yunqian Zhou, Jie He, Nanlin Yin & Hongbo QI

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  1. Youwen Mei
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  2. Yuxin Ran
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  3. Zheng Liu
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Contributions

Youwen Mei and Yuxin Ran designed the study, performed the experiments, analysed the data and wrote the manuscript. Nanlin Yin and Hongbo Qi designed the study, reviewed the manuscript, organised financial support and supervised the project. Zheng Liu, Yunqian Zhou and Jie He performed the experiments and analysed the data. All authors approved the submitted version of the manuscript.

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Correspondence to Nanlin Yin or Hongbo QI.

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Ethics approval was received from the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (2019–137), and written informed consent for participation was obtained from all participants.

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Youwen Mei and Yuxin Ran contributed equally to this work.

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Mei, Y., Ran, Y., Liu, Z. et al. The Role of IL-27 in the Systemic Inflammatory Response That Accompanies Preterm Labour. Inflammation 45, 876–890 (2022). https://doi.org/10.1007/s10753-021-01592-y

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