Dataset Information

Myometrial-derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice.

ABSTRACT: Preterm birth is a major contributor to neonatal mortality and morbidity. Infection results in elevation of inflammation-related cytokines followed by infiltration of immune cells into gestational tissue. CXCL12 levels are elevated in preterm birth indicating it may have a role in preterm labour (PTL); however, the pathophysiological correlations between CXCL12/CXCR4 signalling and premature labour are poorly understood. In this study, PTL was induced using lipopolysaccharide (LPS) in a murine model. LPS induced CXCL12 RNA and protein levels significantly and specifically in myometrium compared with controls (3-fold and 3.5-fold respectively). Highest levels were found just before the start of labour. LPS also enhanced the infiltration of neutrophils, macrophages and T cells, and induced macrophage M1 polarization. In vitro studies showed that condition medium from LPS-treated primary smooth muscle cells (SMC) induced macrophage migration, M1 polarization and upregulated inflammation-related cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNF-α). AMD3100 treatment in pregnant mice led to a significant decrease in the rate of PTL (70%), prolonged pregnancy duration and suppressed macrophage infiltration into gestation tissue by 2.5-fold. Further, in-vitro treatment of SMC by AMD3100 suppressed the macrophage migration, decreased polarization and downregulated IL-1, IL-6 and TNF-α expression. LPS treatment in pregnant mice induced PTL by increasing myometrial CXCL12, which recruits immune cells that in turn produce inflammation-related cytokines. These effects stimulated by LPS were completely reversed by AMD3100 through blocking of CXCL12/CXCR4 signalling. Thus, the CXCL12/CXCR4 axis presents an excellent target for preventing infection and inflammation-related PTL.

SUBMITTER: Zhang L

PROVIDER: S-EPMC9077289 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Myometrial-derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice.

Zhang Lijuan L Mamillapalli Ramanaiah R Habata Shutaro S McAdow Molly M Taylor Hugh S HS

Journal of cellular and molecular medicine 20220323 9

Preterm birth is a major contributor to neonatal mortality and morbidity. Infection results in elevation of inflammation-related cytokines followed by infiltration of immune cells into gestational tissue. CXCL12 levels are elevated in preterm birth indicating it may have a role in preterm labour (PTL); however, the pathophysiological correlations between CXCL12/CXCR4 signalling and premature labour are poorly understood. In this study, PTL was induced using lipopolysaccharide (LPS) in a murine m ...[more]

PMID: 35318804

Similar Datasets

Project description:Comparison of gene expression in labouring and non-labouring myometrium. In this work, gene expression in 48 (22 labouring, 26 non-labouring) myometrial samples was measured using Illumina HT-12 v4.0 BeadChips. Biopsy samples of full thickness lower segment specimens of human myometrium were selected from the Edinburgh Reproductive Tissue Biobank (ERTBB, http://www.crh.ed.ac.uk/biobank/). All tissue samples were collected during Caesarean section from participant tissue donors with informed and written consent, according to the ethical approval and governance granted to the Edinburgh Reproductive Tissues BioBank by the West of Scotland Research Ethics Committee 4 (09/S0704/3). In order to maximise biological replicates on the array, all 22 labouring samples that fulfilled our inclusion criteria and that were stored in the ERTBB as of August 2012 were selected. In order to minimise inter-group variation in baseline characteristics, a second group of non-labouring samples (n=26) were selected by matching to labouring samples on maternal BMI, gestational age, parity and maternal age. We did not exclude smokers or women who had received medication to induce labour. We restricted the number of non-labouring samples to 26 so that all samples (n=48) could fit on three array chips. Forty-five of the samples had been transferred into RNAlater® (Life Technologies, Invitrogen, Carlsbad, CA, USA) immediately after collection and then stored at -80°C. Three labouring samples had not been transferred to RNAlater® before freezing but were also included in the array analysis in order to maximise the number of labouring samples. Total RNA was isolated using TRI Reagent® and the Qiagen RNeasy Lipid Tissue kit protocol (Qiagen, Valencia, CA, USA). The quantity and quality of RNA was assessed using a NanoDrop 1000 (Thermo Scientific, Wilmington, DE, USA). RNA quality was further assessed in the biotin-labelled samples by the Wellcome Trust Clinical Research Facility, Edinburgh using a Bioanalyzer 2100 (Agilent Technologies, Wilmington, DE, USA). To prepare samples for the microarray experiment, 450ng total RNA was amplified and biotin-labelled using the Illumina® TotalPrepTM RNA Amplification Kit (Ambion, Austin, TX, USA). Samples were split randomly over four Illumina HT-12 v4.0 BeadChips to minimise any effect of inter-chip variability. One sample was used per well. The chips were imaged using a BeadArray Reader and raw data was obtained with Illumina BeadStudio software. Raw data were preprocessed using the Lumi package in R version 2.14.1. The data was subjected to Robust Multichip Average (RMA) background correction before quantile normalisation to remove non-biological systematic variation.

Dataset Information

Myometrial-derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice.

Publications

Myometrial-derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets