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Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6

Matthew Turner Orcid Logo, James Cronin Orcid Logo, Gareth Healey Orcid Logo, Iain Martin Sheldon, Martin Sheldon Orcid Logo

Endocrinology, Volume: 155, Issue: 4, Pages: 1453 - 1465

Swansea University Authors: Matthew Turner Orcid Logo, James Cronin Orcid Logo, Gareth Healey Orcid Logo, Martin Sheldon Orcid Logo

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DOI (Published version): 10.1210/en.2013-1822

Abstract

Bacteria often infect the endometrium of cattle to cause endometritis, uterine disease, and infertility. Lipopeptides are commonly found among bacteria and are detected by the Toll-like receptor (TLR) cell surface receptor TLR2 on immune cells. Heterodimers of TLR2 with TLR1 or TLR6 activate MAPK an...

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Published in: Endocrinology
Published: 2014
Online Access: http://press.endocrine.org/doi/pdf/10.1210/en.2013-1822
URI: https://cronfa.swan.ac.uk/Record/cronfa17657
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Lipopeptides are commonly found among bacteria and are detected by the Toll-like receptor (TLR) cell surface receptor TLR2 on immune cells. Heterodimers of TLR2 with TLR1 or TLR6 activate MAPK and nuclear factor-&#x3BA;B intracellular signaling pathways to stimulate inflammatory responses. In the endometrium, epithelial and stromal cells are the first to encounter invading bacteria, so the present study explored whether endometrial cells can also mount inflammatory responses to bacterial lipopeptides via TLRs. The supernatants of pure populations of primary bovine endometrial epithelial and stromal cells accumulated the cytokine IL-6 and the chemokine IL-8 in response to triacylated or diacylated bacterial lipopeptides. The accumulation of IL-6 and IL-8 in response to triacylated lipopeptides was reduced by small interfering RNA targeting TLR2 or TLR1 but not TLR6, whereas cellular responses to diacylated lipopeptide were reduced by small interfering RNA targeting TLR2, TLR1, or TLR6. Both lipopeptides induced rapid phosphorylation of ERK1/2, p38, and nuclear factor-&#x3BA;B in endometrial cells, and inhibitors of ERK1/2 or p38 limited the accumulation of IL-6. The ovarian steroids estradiol and progesterone had little impact on inflammatory responses to lipopeptides. The endometrial epithelial and stromal cell responses to lipopeptides via TLR2, TLR1, and TLR6 provide a mechanism linking a wide range of bacterial infections to inflammation of the endometrium.</abstract><type>Journal Article</type><journal>Endocrinology</journal><volume>155</volume><journalNumber>4</journalNumber><paginationStart>1453</paginationStart><paginationEnd>1465</paginationEnd><publisher/><keywords/><publishedDay>1</publishedDay><publishedMonth>4</publishedMonth><publishedYear>2014</publishedYear><publishedDate>2014-04-01</publishedDate><doi>10.1210/en.2013-1822</doi><url>http://press.endocrine.org/doi/pdf/10.1210/en.2013-1822</url><notes>This work was supported by awards to Sheldon from the UK Biotechnology and Biological Sciences Research Council, and Sheldon's grants supported M.L.T. (BB/F017596/1) and G.D.H. (BB/I017240/1). Turner was a PhD student supervised by Sheldon.</notes><college>COLLEGE NANME</college><department>Medicine</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>PMSC</DepartmentCode><institution>Swansea University</institution><degreesponsorsfunders>BBSRC</degreesponsorsfunders><apcterm/><lastEdited>2019-06-20T17:09:31.0126617</lastEdited><Created>2014-04-01T12:07:31.0456442</Created><path><level id="1">Swansea University Medical School</level><level id="2">Medicine</level></path><authors><author><firstname>Matthew</firstname><surname>Turner</surname><orcid>0000-0002-1369-4051</orcid><order>1</order></author><author><firstname>James</firstname><surname>Cronin</surname><orcid>0000-0002-0590-9462</orcid><order>2</order></author><author><firstname>Gareth</firstname><surname>Healey</surname><orcid>0000-0001-9531-1220</orcid><order>3</order></author><author><firstname>Iain Martin</firstname><surname>Sheldon</surname><order>4</order></author><author><firstname>Martin</firstname><surname>Sheldon</surname><orcid>0000-0001-7902-5558</orcid><order>5</order></author></authors><documents><document><filename>0017657-16062017082753.pdf</filename><originalFilename>TurnerENDO.pdf</originalFilename><uploaded>2017-06-16T08:27:53.7870000</uploaded><type>Output</type><contentLength>1720591</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><embargoDate>2014-04-01T00:00:00.0000000</embargoDate><documentNotes>Distributed under the terms of a Creative Commons Attribution (CC-BY)</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 2019-06-20T17:09:31.0126617 v2 17657 2014-04-01 Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6 d6ee69e43774ed1124d27923140b1e0b 0000-0002-1369-4051 Matthew Turner Matthew Turner true false 9cfd17551c0d1f7438895121e4fbb6e8 0000-0002-0590-9462 James Cronin James Cronin true false 5926519f89187489cfd5e1478aa188b1 0000-0001-9531-1220 Gareth Healey Gareth Healey true false ab0f74b794e59cc270c69e63ee1d9748 0000-0001-7902-5558 Martin Sheldon Martin Sheldon true false 2014-04-01 PMSC Bacteria often infect the endometrium of cattle to cause endometritis, uterine disease, and infertility. Lipopeptides are commonly found among bacteria and are detected by the Toll-like receptor (TLR) cell surface receptor TLR2 on immune cells. Heterodimers of TLR2 with TLR1 or TLR6 activate MAPK and nuclear factor-κB intracellular signaling pathways to stimulate inflammatory responses. In the endometrium, epithelial and stromal cells are the first to encounter invading bacteria, so the present study explored whether endometrial cells can also mount inflammatory responses to bacterial lipopeptides via TLRs. The supernatants of pure populations of primary bovine endometrial epithelial and stromal cells accumulated the cytokine IL-6 and the chemokine IL-8 in response to triacylated or diacylated bacterial lipopeptides. The accumulation of IL-6 and IL-8 in response to triacylated lipopeptides was reduced by small interfering RNA targeting TLR2 or TLR1 but not TLR6, whereas cellular responses to diacylated lipopeptide were reduced by small interfering RNA targeting TLR2, TLR1, or TLR6. Both lipopeptides induced rapid phosphorylation of ERK1/2, p38, and nuclear factor-κB in endometrial cells, and inhibitors of ERK1/2 or p38 limited the accumulation of IL-6. The ovarian steroids estradiol and progesterone had little impact on inflammatory responses to lipopeptides. The endometrial epithelial and stromal cell responses to lipopeptides via TLR2, TLR1, and TLR6 provide a mechanism linking a wide range of bacterial infections to inflammation of the endometrium. Journal Article Endocrinology 155 4 1453 1465 1 4 2014 2014-04-01 10.1210/en.2013-1822 http://press.endocrine.org/doi/pdf/10.1210/en.2013-1822 This work was supported by awards to Sheldon from the UK Biotechnology and Biological Sciences Research Council, and Sheldon's grants supported M.L.T. (BB/F017596/1) and G.D.H. (BB/I017240/1). Turner was a PhD student supervised by Sheldon. COLLEGE NANME Medicine COLLEGE CODE PMSC Swansea University BBSRC 2019-06-20T17:09:31.0126617 2014-04-01T12:07:31.0456442 Swansea University Medical School Medicine Matthew Turner 0000-0002-1369-4051 1 James Cronin 0000-0002-0590-9462 2 Gareth Healey 0000-0001-9531-1220 3 Iain Martin Sheldon 4 Martin Sheldon 0000-0001-7902-5558 5 0017657-16062017082753.pdf TurnerENDO.pdf 2017-06-16T08:27:53.7870000 Output 1720591 application/pdf Version of Record true 2014-04-01T00:00:00.0000000 Distributed under the terms of a Creative Commons Attribution (CC-BY) true eng
title Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
spellingShingle Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
Matthew Turner
James Cronin
Gareth Healey
Martin Sheldon
title_short Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
title_full Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
title_fullStr Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
title_full_unstemmed Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
title_sort Epithelial and Stromal Cells of Bovine Endometrium Have Roles in Innate Immunity and Initiate Inflammatory Responses to Bacterial Lipopeptides In Vitro via Toll-Like Receptors TLR2, TLR1, and TLR6
author_id_str_mv d6ee69e43774ed1124d27923140b1e0b
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author_id_fullname_str_mv d6ee69e43774ed1124d27923140b1e0b_***_Matthew Turner
9cfd17551c0d1f7438895121e4fbb6e8_***_James Cronin
5926519f89187489cfd5e1478aa188b1_***_Gareth Healey
ab0f74b794e59cc270c69e63ee1d9748_***_Martin Sheldon
author Matthew Turner
James Cronin
Gareth Healey
Martin Sheldon
author2 Matthew Turner
James Cronin
Gareth Healey
Iain Martin Sheldon
Martin Sheldon
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container_title Endocrinology
container_volume 155
container_issue 4
container_start_page 1453
publishDate 2014
institution Swansea University
doi_str_mv 10.1210/en.2013-1822
college_str Swansea University Medical School
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hierarchy_top_title Swansea University Medical School
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hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
url http://press.endocrine.org/doi/pdf/10.1210/en.2013-1822
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description Bacteria often infect the endometrium of cattle to cause endometritis, uterine disease, and infertility. Lipopeptides are commonly found among bacteria and are detected by the Toll-like receptor (TLR) cell surface receptor TLR2 on immune cells. Heterodimers of TLR2 with TLR1 or TLR6 activate MAPK and nuclear factor-κB intracellular signaling pathways to stimulate inflammatory responses. In the endometrium, epithelial and stromal cells are the first to encounter invading bacteria, so the present study explored whether endometrial cells can also mount inflammatory responses to bacterial lipopeptides via TLRs. The supernatants of pure populations of primary bovine endometrial epithelial and stromal cells accumulated the cytokine IL-6 and the chemokine IL-8 in response to triacylated or diacylated bacterial lipopeptides. The accumulation of IL-6 and IL-8 in response to triacylated lipopeptides was reduced by small interfering RNA targeting TLR2 or TLR1 but not TLR6, whereas cellular responses to diacylated lipopeptide were reduced by small interfering RNA targeting TLR2, TLR1, or TLR6. Both lipopeptides induced rapid phosphorylation of ERK1/2, p38, and nuclear factor-κB in endometrial cells, and inhibitors of ERK1/2 or p38 limited the accumulation of IL-6. The ovarian steroids estradiol and progesterone had little impact on inflammatory responses to lipopeptides. The endometrial epithelial and stromal cell responses to lipopeptides via TLR2, TLR1, and TLR6 provide a mechanism linking a wide range of bacterial infections to inflammation of the endometrium.
published_date 2014-04-01T03:34:38Z
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