Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin
The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic Escherichia coli (UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infec...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2020-05, Vol.10 (1), p.8473, Article 8473 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | 8473 |
| container_title | Scientific reports |
| container_volume | 10 |
| creator | Stanton, Anna Mowbray, Catherine Lanz, Marcelo Brown, Karen Hilton, Paul Tyson-Capper, Alison Pickard, Robert S. Ali, Ased S. M. Hall, Judith |
| description | The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic
Escherichia coli
(UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate,
in vitro
, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with
E.coli
flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml
E.coli
flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including
DEFβ4A
,
DEFB103A
,
LCN2
as well as those associated with keratinisation eg
CNFN
and
SPRR
family genes were significantly enhanced (P |
| doi_str_mv | 10.1038/s41598-020-64291-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7242342</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2405596457</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-3afbf0b8d7b449f92a24ac5e606ecf90411159cb2851c7b679ea122af15e692f3</originalsourceid><addsrcrecordid>eNp9kVFLwzAQx4Mobsx9AR-k4HM1uSZt8yKMsakwEGTuNaRZ2mV0zUw6Yd_ezM6pL4bABe53_7vLH6Frgu8ITvJ7TwnjeYwBxykFTuL9GeoDpiyGBOD817uHht6vcTgMOCX8EvUSoAnPGeujxdxujZJ1NPGts5VuornTst3opo1Gu-oQfdSudLSQlWkC96r91jZeR60NNWqlnVErIyNlaxNNa1npujbNFbooZe318BgH6G06mY-f4tnL4_N4NIsVzWgbJ7IsSlzky6yglJccJFCpmE5xqlXJMSUkbKkKyBlRWZFmXEsCIEsSGA5lMkAPne52V2z0UoVxnazF1pmNdHthpRF_M41Zicp-iAwoJOEO0O1RwNn3nfatWNudC4t6ARQzxlPKskBBRylnvXe6PHUgWBzsEJ0dItghvuwQ-1B083u2U8n35wcg6QAfUk2l3U_vf2Q_AZiWl48</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2405596457</pqid></control><display><type>article</type><title>Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Stanton, Anna ; Mowbray, Catherine ; Lanz, Marcelo ; Brown, Karen ; Hilton, Paul ; Tyson-Capper, Alison ; Pickard, Robert S. ; Ali, Ased S. M. ; Hall, Judith</creator><creatorcontrib>Stanton, Anna ; Mowbray, Catherine ; Lanz, Marcelo ; Brown, Karen ; Hilton, Paul ; Tyson-Capper, Alison ; Pickard, Robert S. ; Ali, Ased S. M. ; Hall, Judith</creatorcontrib><description>The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic
Escherichia coli
(UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate,
in vitro
, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with
E.coli
flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml
E.coli
flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including
DEFβ4A
,
DEFB103A
,
LCN2
as well as those associated with keratinisation eg
CNFN
and
SPRR
family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the
DEFβ4
gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced
DEFβ4, DEF103A
and
S100A7
expression (P < 0.05). Origins of vaginal IL-17
in vivo
remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-64291-y</identifier><identifier>PMID: 32439855</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/106 ; 13/21 ; 17β-Estradiol ; 38 ; 38/39 ; 45 ; 45/61 ; 692/4025/2768/1865 ; 692/699/2768/1865 ; 82 ; Administration, Topical ; DNA microarrays ; E coli ; Epithelial cells ; Epithelium ; Escherichia coli ; Escherichia coli Proteins - genetics ; Escherichia coli Proteins - metabolism ; Estrogen receptors ; Estrogens ; Estrogens - administration & dosage ; Female ; Flagellin ; Flagellin - genetics ; Flagellin - metabolism ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation - drug effects ; Humanities and Social Sciences ; Humans ; Inflammation ; Interleukin 17 ; Lymphocytes T ; Menopause ; Middle Aged ; Mimicry ; multidisciplinary ; Ribonucleic acid ; RNA ; Science ; Science (multidisciplinary) ; Signal transduction ; Toll-like receptors ; Urinary tract ; Vagina ; Vagina - drug effects ; Vagina - metabolism ; Vagina - physiology</subject><ispartof>Scientific reports, 2020-05, Vol.10 (1), p.8473, Article 8473</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-3afbf0b8d7b449f92a24ac5e606ecf90411159cb2851c7b679ea122af15e692f3</citedby><cites>FETCH-LOGICAL-c474t-3afbf0b8d7b449f92a24ac5e606ecf90411159cb2851c7b679ea122af15e692f3</cites><orcidid>0000-0001-8234-0276 ; 0000-0002-2541-5195</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242342/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242342/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51555,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32439855$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stanton, Anna</creatorcontrib><creatorcontrib>Mowbray, Catherine</creatorcontrib><creatorcontrib>Lanz, Marcelo</creatorcontrib><creatorcontrib>Brown, Karen</creatorcontrib><creatorcontrib>Hilton, Paul</creatorcontrib><creatorcontrib>Tyson-Capper, Alison</creatorcontrib><creatorcontrib>Pickard, Robert S.</creatorcontrib><creatorcontrib>Ali, Ased S. M.</creatorcontrib><creatorcontrib>Hall, Judith</creatorcontrib><title>Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic
Escherichia coli
(UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate,
in vitro
, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with
E.coli
flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml
E.coli
flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including
DEFβ4A
,
DEFB103A
,
LCN2
as well as those associated with keratinisation eg
CNFN
and
SPRR
family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the
DEFβ4
gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced
DEFβ4, DEF103A
and
S100A7
expression (P < 0.05). Origins of vaginal IL-17
in vivo
remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application.</description><subject>13</subject><subject>13/106</subject><subject>13/21</subject><subject>17β-Estradiol</subject><subject>38</subject><subject>38/39</subject><subject>45</subject><subject>45/61</subject><subject>692/4025/2768/1865</subject><subject>692/699/2768/1865</subject><subject>82</subject><subject>Administration, Topical</subject><subject>DNA microarrays</subject><subject>E coli</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Escherichia coli</subject><subject>Escherichia coli Proteins - genetics</subject><subject>Escherichia coli Proteins - metabolism</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Estrogens - administration & dosage</subject><subject>Female</subject><subject>Flagellin</subject><subject>Flagellin - genetics</subject><subject>Flagellin - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 17</subject><subject>Lymphocytes T</subject><subject>Menopause</subject><subject>Middle Aged</subject><subject>Mimicry</subject><subject>multidisciplinary</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal transduction</subject><subject>Toll-like receptors</subject><subject>Urinary tract</subject><subject>Vagina</subject><subject>Vagina - drug effects</subject><subject>Vagina - metabolism</subject><subject>Vagina - physiology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kVFLwzAQx4Mobsx9AR-k4HM1uSZt8yKMsakwEGTuNaRZ2mV0zUw6Yd_ezM6pL4bABe53_7vLH6Frgu8ITvJ7TwnjeYwBxykFTuL9GeoDpiyGBOD817uHht6vcTgMOCX8EvUSoAnPGeujxdxujZJ1NPGts5VuornTst3opo1Gu-oQfdSudLSQlWkC96r91jZeR60NNWqlnVErIyNlaxNNa1npujbNFbooZe318BgH6G06mY-f4tnL4_N4NIsVzWgbJ7IsSlzky6yglJccJFCpmE5xqlXJMSUkbKkKyBlRWZFmXEsCIEsSGA5lMkAPne52V2z0UoVxnazF1pmNdHthpRF_M41Zicp-iAwoJOEO0O1RwNn3nfatWNudC4t6ARQzxlPKskBBRylnvXe6PHUgWBzsEJ0dItghvuwQ-1B083u2U8n35wcg6QAfUk2l3U_vf2Q_AZiWl48</recordid><startdate>20200521</startdate><enddate>20200521</enddate><creator>Stanton, Anna</creator><creator>Mowbray, Catherine</creator><creator>Lanz, Marcelo</creator><creator>Brown, Karen</creator><creator>Hilton, Paul</creator><creator>Tyson-Capper, Alison</creator><creator>Pickard, Robert S.</creator><creator>Ali, Ased S. M.</creator><creator>Hall, Judith</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8234-0276</orcidid><orcidid>https://orcid.org/0000-0002-2541-5195</orcidid></search><sort><creationdate>20200521</creationdate><title>Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin</title><author>Stanton, Anna ; Mowbray, Catherine ; Lanz, Marcelo ; Brown, Karen ; Hilton, Paul ; Tyson-Capper, Alison ; Pickard, Robert S. ; Ali, Ased S. M. ; Hall, Judith</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-3afbf0b8d7b449f92a24ac5e606ecf90411159cb2851c7b679ea122af15e692f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13</topic><topic>13/106</topic><topic>13/21</topic><topic>17β-Estradiol</topic><topic>38</topic><topic>38/39</topic><topic>45</topic><topic>45/61</topic><topic>692/4025/2768/1865</topic><topic>692/699/2768/1865</topic><topic>82</topic><topic>Administration, Topical</topic><topic>DNA microarrays</topic><topic>E coli</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Escherichia coli</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Escherichia coli Proteins - metabolism</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Estrogens - administration & dosage</topic><topic>Female</topic><topic>Flagellin</topic><topic>Flagellin - genetics</topic><topic>Flagellin - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 17</topic><topic>Lymphocytes T</topic><topic>Menopause</topic><topic>Middle Aged</topic><topic>Mimicry</topic><topic>multidisciplinary</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal transduction</topic><topic>Toll-like receptors</topic><topic>Urinary tract</topic><topic>Vagina</topic><topic>Vagina - drug effects</topic><topic>Vagina - metabolism</topic><topic>Vagina - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stanton, Anna</creatorcontrib><creatorcontrib>Mowbray, Catherine</creatorcontrib><creatorcontrib>Lanz, Marcelo</creatorcontrib><creatorcontrib>Brown, Karen</creatorcontrib><creatorcontrib>Hilton, Paul</creatorcontrib><creatorcontrib>Tyson-Capper, Alison</creatorcontrib><creatorcontrib>Pickard, Robert S.</creatorcontrib><creatorcontrib>Ali, Ased S. M.</creatorcontrib><creatorcontrib>Hall, Judith</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stanton, Anna</au><au>Mowbray, Catherine</au><au>Lanz, Marcelo</au><au>Brown, Karen</au><au>Hilton, Paul</au><au>Tyson-Capper, Alison</au><au>Pickard, Robert S.</au><au>Ali, Ased S. M.</au><au>Hall, Judith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-05-21</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>8473</spage><pages>8473-</pages><artnum>8473</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic
Escherichia coli
(UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate,
in vitro
, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with
E.coli
flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml
E.coli
flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including
DEFβ4A
,
DEFB103A
,
LCN2
as well as those associated with keratinisation eg
CNFN
and
SPRR
family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the
DEFβ4
gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced
DEFβ4, DEF103A
and
S100A7
expression (P < 0.05). Origins of vaginal IL-17
in vivo
remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32439855</pmid><doi>10.1038/s41598-020-64291-y</doi><orcidid>https://orcid.org/0000-0001-8234-0276</orcidid><orcidid>https://orcid.org/0000-0002-2541-5195</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2020-05, Vol.10 (1), p.8473, Article 8473 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7242342 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 13 13/106 13/21 17β-Estradiol 38 38/39 45 45/61 692/4025/2768/1865 692/699/2768/1865 82 Administration, Topical DNA microarrays E coli Epithelial cells Epithelium Escherichia coli Escherichia coli Proteins - genetics Escherichia coli Proteins - metabolism Estrogen receptors Estrogens Estrogens - administration & dosage Female Flagellin Flagellin - genetics Flagellin - metabolism Gene expression Gene Expression Profiling Gene Expression Regulation - drug effects Humanities and Social Sciences Humans Inflammation Interleukin 17 Lymphocytes T Menopause Middle Aged Mimicry multidisciplinary Ribonucleic acid RNA Science Science (multidisciplinary) Signal transduction Toll-like receptors Urinary tract Vagina Vagina - drug effects Vagina - metabolism Vagina - physiology |
| title | Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T22%3A22%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Topical%20Estrogen%20Treatment%20Augments%20the%20Vaginal%20Response%20to%20Escherichia%20coli%20Flagellin&rft.jtitle=Scientific%20reports&rft.au=Stanton,%20Anna&rft.date=2020-05-21&rft.volume=10&rft.issue=1&rft.spage=8473&rft.pages=8473-&rft.artnum=8473&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-64291-y&rft_dat=%3Cproquest_pubme%3E2405596457%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2405596457&rft_id=info:pmid/32439855&rfr_iscdi=true |