IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway

Spontaneous preterm birth (sPTB), defined as delivery before 37 weeks of gestation, is thought to be a multifactorial syndrome. However, the inflammatory imbalance at the maternal-fetal interface promotes excessive secretion of inflammatory factors and induces apoptosis and degradation of the extrac...

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Main Authors: Lulu Wang, Zheng Liu, Dongni Huang, Yuxin Ran, Hanwen Zhang, Jie He, Nanlin Yin, Hongbo Qi
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/1069563
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author Lulu Wang
Zheng Liu
Dongni Huang
Yuxin Ran
Hanwen Zhang
Jie He
Nanlin Yin
Hongbo Qi
author_facet Lulu Wang
Zheng Liu
Dongni Huang
Yuxin Ran
Hanwen Zhang
Jie He
Nanlin Yin
Hongbo Qi
author_sort Lulu Wang
collection DOAJ
description Spontaneous preterm birth (sPTB), defined as delivery before 37 weeks of gestation, is thought to be a multifactorial syndrome. However, the inflammatory imbalance at the maternal-fetal interface promotes excessive secretion of inflammatory factors and induces apoptosis and degradation of the extracellular matrix (ECM), which can subsequently lead to preterm birth. As an anti-inflammatory molecule in the IL-1 family, interleukin-37 (IL-37) mainly plays an inhibiting role in a variety of inflammatory diseases. However, as a typical inflammatory disease, no previous studies have been carried out to explore the role of IL-37 in sPTB. In this study, a series of molecular biological experiments were performed in clinical samples and human amniotic epithelial cell line (Wistar Institute Susan Hayflick (WISH)) to investigate the deficiency role of IL-37 and the potential mechanism. Firstly, the results indicated that the expression of IL-37 in human peripheral plasma and fetal membranes was significantly decreased in the sPTB group. Afterward, it is proved that IL-37 could significantly suppress the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in WISH cells. Simultaneously, once silence IL-37, LPS-induced apoptosis and activity of matrix metalloproteinases (MMPs) 2 and 9 were significantly increased. In addition, the western blot data showed that IL-37 performed its biological effects by inhibiting the NF-κB and IL-6/STAT3 pathway. In conclusion, our results suggest that IL-37 limits excessive inflammation and subsequently inhibits ECM remodeling and apoptosis through the NF-κB and IL-6/STAT3 signaling pathway in the fetal membranes.
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spelling doaj-art-ba287bfb36e94819ba06775802b53ff22025-08-20T02:19:26ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/10695631069563IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling PathwayLulu Wang0Zheng Liu1Dongni Huang2Yuxin Ran3Hanwen Zhang4Jie He5Nanlin Yin6Hongbo Qi7Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaSpontaneous preterm birth (sPTB), defined as delivery before 37 weeks of gestation, is thought to be a multifactorial syndrome. However, the inflammatory imbalance at the maternal-fetal interface promotes excessive secretion of inflammatory factors and induces apoptosis and degradation of the extracellular matrix (ECM), which can subsequently lead to preterm birth. As an anti-inflammatory molecule in the IL-1 family, interleukin-37 (IL-37) mainly plays an inhibiting role in a variety of inflammatory diseases. However, as a typical inflammatory disease, no previous studies have been carried out to explore the role of IL-37 in sPTB. In this study, a series of molecular biological experiments were performed in clinical samples and human amniotic epithelial cell line (Wistar Institute Susan Hayflick (WISH)) to investigate the deficiency role of IL-37 and the potential mechanism. Firstly, the results indicated that the expression of IL-37 in human peripheral plasma and fetal membranes was significantly decreased in the sPTB group. Afterward, it is proved that IL-37 could significantly suppress the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in WISH cells. Simultaneously, once silence IL-37, LPS-induced apoptosis and activity of matrix metalloproteinases (MMPs) 2 and 9 were significantly increased. In addition, the western blot data showed that IL-37 performed its biological effects by inhibiting the NF-κB and IL-6/STAT3 pathway. In conclusion, our results suggest that IL-37 limits excessive inflammation and subsequently inhibits ECM remodeling and apoptosis through the NF-κB and IL-6/STAT3 signaling pathway in the fetal membranes.http://dx.doi.org/10.1155/2020/1069563
spellingShingle Lulu Wang
Zheng Liu
Dongni Huang
Yuxin Ran
Hanwen Zhang
Jie He
Nanlin Yin
Hongbo Qi
IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway
Mediators of Inflammation
title IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway
title_full IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway
title_fullStr IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway
title_full_unstemmed IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway
title_short IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway
title_sort il 37 exerts anti inflammatory effects in fetal membranes of spontaneous preterm birth via the nf κb and il 6 stat3 signaling pathway
url http://dx.doi.org/10.1155/2020/1069563
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