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Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta

Shalini Patni, Aled Bryant Orcid Logo, Louise P. Wynen, Anna L. Seager, Gareth Morgan, Cathy Thornton Orcid Logo

Placenta, Volume: 36, Issue: 9, Pages: 1031 - 1038

Swansea University Authors: Aled Bryant Orcid Logo, Cathy Thornton Orcid Logo

DOI (Published version): 10.1016/j.placenta.2015.06.017

Abstract

INTRODUCTION: Toll-like receptor (TLR) activity within gestation-associated tissues might have a role in normal pregnancy progression as well as adverse obstetric outcomes such as preterm birth (PTB). METHODS: The expression and activity of TLRs 1 – 9 in placentas collected following preterm vaginal...

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Published in: Placenta
Published: 2015
URI: https://cronfa.swan.ac.uk/Record/cronfa23518
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spelling 2017-01-23T14:18:24.7009311 v2 23518 2015-09-30 Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta 021f7adc0923f6d2c2e2fc269758b8fe 0000-0002-4650-4672 Aled Bryant Aled Bryant true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false 2015-09-30 PMSC INTRODUCTION: Toll-like receptor (TLR) activity within gestation-associated tissues might have a role in normal pregnancy progression as well as adverse obstetric outcomes such as preterm birth (PTB). METHODS: The expression and activity of TLRs 1 – 9 in placentas collected following preterm vaginal delivery after infection-associated preterm labour (IA-PTL) at 25 – 36 weeks of gestation (preterm-svd, n = 10) were compared with those obtained after normal vaginal delivery at term (term-laboured; n=17). Placental explants were cultured in the presence of agonists for TLR2, 3, 4, 5, 7, 8 and 9 and cytokine production after 24 hours examined. Expression of TLR transcripts was determined using real time quantitative PCR. RESULTS: Reactivity to all agonists except CpG oligonucleotides was observed indicating that other than TLR9 all of the receptors studied yielded functional responses both term and preterm. Significantly less TNFα and IL-6, but not IL-10, were produced by preterm than term samples in response to all TLR agonists. Changes in TLR mRNA expression did not underlie functional differences in the preterm and term groups; nor does a pre-exposure/tolerance model mimic this finding. While glucocorticoids suppressed cytokine production in an in vitro model using term tissue the association between lower gestational age and decreased cytokine outputs suggests a temporally regulated response. DISCUSSION: Pro-inflammatory cytokine output in response to multiple TLR ligands was decreased in the preterm compared to the term placenta but gene expression for each TLR tended to be similar. Reduced cytokine production by the preterm placenta in response to stimulation of TLRs therefore must be regulated at the post-transcriptional level in a gestational age dependent manner. Journal Article Placenta 36 9 1031 1038 11 7 2015 2015-07-11 10.1016/j.placenta.2015.06.017 COLLEGE NANME Medicine COLLEGE CODE PMSC Swansea University 2017-01-23T14:18:24.7009311 2015-09-30T12:36:42.8934678 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Shalini Patni 1 Aled Bryant 0000-0002-4650-4672 2 Louise P. Wynen 3 Anna L. Seager 4 Gareth Morgan 5 Cathy Thornton 0000-0002-5153-573X 6 0023518-14012016091441.pdf PatnietalPTBPaperacceptedversion.pdf 2016-01-14T09:14:41.0530000 Output 384476 application/pdf Accepted Manuscript true 2016-07-31T00:00:00.0000000 true
title Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
spellingShingle Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
Aled Bryant
Cathy Thornton
title_short Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
title_full Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
title_fullStr Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
title_full_unstemmed Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
title_sort Functional activity but not gene expression of toll-like receptors is decreased in the preterm versus term human placenta
author_id_str_mv 021f7adc0923f6d2c2e2fc269758b8fe
c71a7a4be7361094d046d312202bce0c
author_id_fullname_str_mv 021f7adc0923f6d2c2e2fc269758b8fe_***_Aled Bryant
c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton
author Aled Bryant
Cathy Thornton
author2 Shalini Patni
Aled Bryant
Louise P. Wynen
Anna L. Seager
Gareth Morgan
Cathy Thornton
format Journal article
container_title Placenta
container_volume 36
container_issue 9
container_start_page 1031
publishDate 2015
institution Swansea University
doi_str_mv 10.1016/j.placenta.2015.06.017
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description INTRODUCTION: Toll-like receptor (TLR) activity within gestation-associated tissues might have a role in normal pregnancy progression as well as adverse obstetric outcomes such as preterm birth (PTB). METHODS: The expression and activity of TLRs 1 – 9 in placentas collected following preterm vaginal delivery after infection-associated preterm labour (IA-PTL) at 25 – 36 weeks of gestation (preterm-svd, n = 10) were compared with those obtained after normal vaginal delivery at term (term-laboured; n=17). Placental explants were cultured in the presence of agonists for TLR2, 3, 4, 5, 7, 8 and 9 and cytokine production after 24 hours examined. Expression of TLR transcripts was determined using real time quantitative PCR. RESULTS: Reactivity to all agonists except CpG oligonucleotides was observed indicating that other than TLR9 all of the receptors studied yielded functional responses both term and preterm. Significantly less TNFα and IL-6, but not IL-10, were produced by preterm than term samples in response to all TLR agonists. Changes in TLR mRNA expression did not underlie functional differences in the preterm and term groups; nor does a pre-exposure/tolerance model mimic this finding. While glucocorticoids suppressed cytokine production in an in vitro model using term tissue the association between lower gestational age and decreased cytokine outputs suggests a temporally regulated response. DISCUSSION: Pro-inflammatory cytokine output in response to multiple TLR ligands was decreased in the preterm compared to the term placenta but gene expression for each TLR tended to be similar. Reduced cytokine production by the preterm placenta in response to stimulation of TLRs therefore must be regulated at the post-transcriptional level in a gestational age dependent manner.
published_date 2015-07-11T03:27:44Z
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