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

  • Inflammation. 2022 Apr;45(2):876-890. doi: 10.1007/s10753-021-01592-y.
Youwen Mei  1  2  3 Yuxin Ran  1  2  3 Zheng Liu  1  2  3 Yunqian Zhou  1  2  3 Jie He  1  2  3 Nanlin Yin  4  5  6 Hongbo Qi  7  8  9
Affiliations
  • 1. International Collaborative Jointed Laboratory of Maternal and Fetal Medicine, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
  • 2. State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China.
  • 3. Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 4. International Collaborative Jointed Laboratory of Maternal and Fetal Medicine, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. [email protected].
  • 5. State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China. [email protected].
  • 6. Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. [email protected].
  • 7. International Collaborative Jointed Laboratory of Maternal and Fetal Medicine, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. [email protected].
  • 8. State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China. [email protected].
  • 9. Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. [email protected].
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.

Keywords
amniotic epithelial cell.; interleukin-27; peripheral blood mononuclear cells; preterm labour.
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