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Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways

Jennifer C. Price, John J. Bromfield, I. Martin Sheldon, Martin Sheldon Orcid Logo

Endocrinology, Volume: 154, Issue: 9, Pages: 3377 - 3386

Swansea University Author: Martin Sheldon Orcid Logo

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DOI (Published version): 10.1210/en.2013-1102

Abstract

Bacterial infections of the uterus or mammary gland commonly cause disease and infertility byperturbing growth and steroidogenesis of the dominant follicle in the ovary of cattle. Cells of theinnate immune system use Toll-like receptors TLR2, TLR4 and TLR5 to recognize pathogen-associatedmolecular p...

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Published in: Endocrinology
ISSN: 0013-7227 1945-7170
Published: 2013
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URI: https://cronfa.swan.ac.uk/Record/cronfa15414
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first_indexed 2013-08-22T01:57:48Z
last_indexed 2018-05-24T18:11:34Z
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spelling 2018-05-24T14:20:59.4191592 v2 15414 2013-08-09 Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways ab0f74b794e59cc270c69e63ee1d9748 0000-0001-7902-5558 Martin Sheldon Martin Sheldon true false 2013-08-09 BMS Bacterial infections of the uterus or mammary gland commonly cause disease and infertility byperturbing growth and steroidogenesis of the dominant follicle in the ovary of cattle. Cells of theinnate immune system use Toll-like receptors TLR2, TLR4 and TLR5 to recognize pathogen-associatedmolecular patterns (PAMPs) expressed by bacteria, leading to activation of MAPK and NFBpathways, and production of inflammatory cytokines such as IL-1 and IL-6, and the chemokineIL-8. The present study tested whether granulosa cells from dominant follicles have functionalTLR2, TLR4 and TLR5 pathways. Supernatants of primary bovine granulosa cells accumulated IL-1,IL-6andIL-8whentreated for 24hwithPAMthat binds TLR2 or LPS that binds TLR4, but not flagellinthat binds TLR5. Granulosa cell responses to PAM or LPS were rapid, with increased phosphorylationof p38 and ERK1/2 within 30 min and increased abundance of IL6, IL1B, IL10, TNF, IL8 andCCL5 mRNA after 3 h treatment. Accumulation of IL-6 in response to PAM and LPS was attenuatedusing siRNA targeting TLR2 and TLR4, respectively. Furthermore, treating granulosa cells withinhibitors targeting MAPK or NFB reduced the accumulation of IL-6 in response to LPS or PAM.Treatment with LPS or PAM reduced the accumulation of estradiol and progesterone, and thePAMPs reduced granulosa cell expression of CYP19A1 mRNA and protein. In conclusion, bacterialPAMPs initiate inflammation and perturb the endocrine function of bovine granulosa cells fromdominant follicles via TLR2 and TLR4 pathways. Journal Article Endocrinology 154 9 3377 3386 0013-7227 1945-7170 Ovary Infection Immunity 3 7 2013 2013-07-03 10.1210/en.2013-1102 http://endo.endojournals.org/content/early/2013/07/02/en.2013-1102.abstract COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2018-05-24T14:20:59.4191592 2013-08-09T08:46:44.5824665 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Jennifer C. Price 1 John J. Bromfield 2 I. Martin Sheldon 3 Martin Sheldon 0000-0001-7902-5558 4
title Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
spellingShingle Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
Martin Sheldon
title_short Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
title_full Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
title_fullStr Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
title_full_unstemmed Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
title_sort Pathogen-Associated Molecular Patterns Initiate Inflammation and Perturb the Endocrine Function of Bovine Granulosa Cells From Ovarian Dominant Follicles via TLR2 and TLR4 Pathways
author_id_str_mv ab0f74b794e59cc270c69e63ee1d9748
author_id_fullname_str_mv ab0f74b794e59cc270c69e63ee1d9748_***_Martin Sheldon
author Martin Sheldon
author2 Jennifer C. Price
John J. Bromfield
I. Martin Sheldon
Martin Sheldon
format Journal article
container_title Endocrinology
container_volume 154
container_issue 9
container_start_page 3377
publishDate 2013
institution Swansea University
issn 0013-7227
1945-7170
doi_str_mv 10.1210/en.2013-1102
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
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
url http://endo.endojournals.org/content/early/2013/07/02/en.2013-1102.abstract
document_store_str 0
active_str 0
description Bacterial infections of the uterus or mammary gland commonly cause disease and infertility byperturbing growth and steroidogenesis of the dominant follicle in the ovary of cattle. Cells of theinnate immune system use Toll-like receptors TLR2, TLR4 and TLR5 to recognize pathogen-associatedmolecular patterns (PAMPs) expressed by bacteria, leading to activation of MAPK and NFBpathways, and production of inflammatory cytokines such as IL-1 and IL-6, and the chemokineIL-8. The present study tested whether granulosa cells from dominant follicles have functionalTLR2, TLR4 and TLR5 pathways. Supernatants of primary bovine granulosa cells accumulated IL-1,IL-6andIL-8whentreated for 24hwithPAMthat binds TLR2 or LPS that binds TLR4, but not flagellinthat binds TLR5. Granulosa cell responses to PAM or LPS were rapid, with increased phosphorylationof p38 and ERK1/2 within 30 min and increased abundance of IL6, IL1B, IL10, TNF, IL8 andCCL5 mRNA after 3 h treatment. Accumulation of IL-6 in response to PAM and LPS was attenuatedusing siRNA targeting TLR2 and TLR4, respectively. Furthermore, treating granulosa cells withinhibitors targeting MAPK or NFB reduced the accumulation of IL-6 in response to LPS or PAM.Treatment with LPS or PAM reduced the accumulation of estradiol and progesterone, and thePAMPs reduced granulosa cell expression of CYP19A1 mRNA and protein. In conclusion, bacterialPAMPs initiate inflammation and perturb the endocrine function of bovine granulosa cells fromdominant follicles via TLR2 and TLR4 pathways.
published_date 2013-07-03T03:17:34Z
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