miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli
Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (...
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| Veröffentlicht in: | Scientific reports 2018-11, Vol.8 (1), p.17350-12, Article 17350 |
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| creator | Anzola, Andrea González, Raquel Gámez-Belmonte, Reyes Ocón, Borja Aranda, Carlos J. Martínez-Moya, Patricia López-Posadas, Rocío Hernández-Chirlaque, Cristina Sánchez de Medina, Fermín Martínez-Augustin, Olga |
| description | Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1β/TNF) stimulate miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1β (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota. |
| doi_str_mv | 10.1038/s41598-018-35338-y |
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Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1β/TNF) stimulate miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1β (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-35338-y</identifier><identifier>PMID: 30478292</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 14 ; 38/109 ; 38/77 ; 38/89 ; 38/90 ; 631/250/256/2515 ; 631/250/262/2106/2108 ; 631/337/505 ; 64 ; 64/110 ; 64/60 ; 96 ; AKT protein ; Animal models ; Animals ; Antigens ; CD4 antigen ; Cell Line ; Colitis ; Colitis - chemically induced ; Colitis - genetics ; Colitis - immunology ; Colitis - pathology ; Colon ; CpG islands ; Dextran ; Dextran sulfate ; Epithelial cells ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelium ; Female ; Flagellin - toxicity ; Gastrointestinal Microbiome - genetics ; Homeodomain Proteins - genetics ; Humanities and Social Sciences ; Humans ; Immunological tolerance ; Inflammation ; Interleukin 8 ; Intestine ; Intestines - cytology ; Intestines - microbiology ; L-selectin ; Lipopolysaccharides ; Lipopolysaccharides - toxicity ; Lymphocytes ; Lymphocytes T ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Monocyte chemoattractant protein 1 ; multidisciplinary ; MyD88 protein ; Myeloid Differentiation Factor 88 - genetics ; Myeloid Differentiation Factor 88 - metabolism ; NF-κB protein ; Peptidoglycans ; Rats, Wistar ; Rodents ; Science ; Science (multidisciplinary) ; Sodium ; TLR2 protein ; TLR4 protein ; Toll-Like Receptor 2 - genetics ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors</subject><ispartof>Scientific reports, 2018-11, Vol.8 (1), p.17350-12, Article 17350</ispartof><rights>The Author(s) 2018</rights><rights>2018. 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-718ea1a71c765cdabbceeccff34606fc9d9b0bd16ce67110a4663119ebd3eddd3</citedby><cites>FETCH-LOGICAL-c474t-718ea1a71c765cdabbceeccff34606fc9d9b0bd16ce67110a4663119ebd3eddd3</cites><orcidid>0000-0002-4516-5824 ; 0000-0001-8291-3468 ; 0000-0001-9795-6962</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/PMC6255912/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255912/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30478292$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anzola, Andrea</creatorcontrib><creatorcontrib>González, Raquel</creatorcontrib><creatorcontrib>Gámez-Belmonte, Reyes</creatorcontrib><creatorcontrib>Ocón, Borja</creatorcontrib><creatorcontrib>Aranda, Carlos J.</creatorcontrib><creatorcontrib>Martínez-Moya, Patricia</creatorcontrib><creatorcontrib>López-Posadas, Rocío</creatorcontrib><creatorcontrib>Hernández-Chirlaque, Cristina</creatorcontrib><creatorcontrib>Sánchez de Medina, Fermín</creatorcontrib><creatorcontrib>Martínez-Augustin, Olga</creatorcontrib><title>miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1β/TNF) stimulate miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1β (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota.</description><subject>13</subject><subject>14</subject><subject>38/109</subject><subject>38/77</subject><subject>38/89</subject><subject>38/90</subject><subject>631/250/256/2515</subject><subject>631/250/262/2106/2108</subject><subject>631/337/505</subject><subject>64</subject><subject>64/110</subject><subject>64/60</subject><subject>96</subject><subject>AKT protein</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens</subject><subject>CD4 antigen</subject><subject>Cell Line</subject><subject>Colitis</subject><subject>Colitis - chemically induced</subject><subject>Colitis - genetics</subject><subject>Colitis - immunology</subject><subject>Colitis - pathology</subject><subject>Colon</subject><subject>CpG islands</subject><subject>Dextran</subject><subject>Dextran sulfate</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelium</subject><subject>Female</subject><subject>Flagellin - toxicity</subject><subject>Gastrointestinal Microbiome - genetics</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunological tolerance</subject><subject>Inflammation</subject><subject>Interleukin 8</subject><subject>Intestine</subject><subject>Intestines - cytology</subject><subject>Intestines - microbiology</subject><subject>L-selectin</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - toxicity</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Monocyte chemoattractant protein 1</subject><subject>multidisciplinary</subject><subject>MyD88 protein</subject><subject>Myeloid Differentiation Factor 88 - 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chemically induced</topic><topic>Colitis - genetics</topic><topic>Colitis - immunology</topic><topic>Colitis - pathology</topic><topic>Colon</topic><topic>CpG islands</topic><topic>Dextran</topic><topic>Dextran sulfate</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelium</topic><topic>Female</topic><topic>Flagellin - toxicity</topic><topic>Gastrointestinal Microbiome - genetics</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Immunological tolerance</topic><topic>Inflammation</topic><topic>Interleukin 8</topic><topic>Intestine</topic><topic>Intestines - cytology</topic><topic>Intestines - microbiology</topic><topic>L-selectin</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - toxicity</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Monocyte chemoattractant protein 1</topic><topic>multidisciplinary</topic><topic>MyD88 protein</topic><topic>Myeloid Differentiation Factor 88 - genetics</topic><topic>Myeloid Differentiation Factor 88 - metabolism</topic><topic>NF-κB protein</topic><topic>Peptidoglycans</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sodium</topic><topic>TLR2 protein</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 2 - genetics</topic><topic>Toll-Like Receptor 4 - genetics</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anzola, Andrea</creatorcontrib><creatorcontrib>González, Raquel</creatorcontrib><creatorcontrib>Gámez-Belmonte, Reyes</creatorcontrib><creatorcontrib>Ocón, Borja</creatorcontrib><creatorcontrib>Aranda, Carlos J.</creatorcontrib><creatorcontrib>Martínez-Moya, Patricia</creatorcontrib><creatorcontrib>López-Posadas, Rocío</creatorcontrib><creatorcontrib>Hernández-Chirlaque, Cristina</creatorcontrib><creatorcontrib>Sánchez de Medina, Fermín</creatorcontrib><creatorcontrib>Martínez-Augustin, Olga</creatorcontrib><collection>SpringerOpen</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>ProQuest 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)</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>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Science Journals</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>MEDLINE - Academic</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>Anzola, Andrea</au><au>González, Raquel</au><au>Gámez-Belmonte, Reyes</au><au>Ocón, Borja</au><au>Aranda, Carlos J.</au><au>Martínez-Moya, Patricia</au><au>López-Posadas, Rocío</au><au>Hernández-Chirlaque, Cristina</au><au>Sánchez de Medina, Fermín</au><au>Martínez-Augustin, Olga</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2018-11-26</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>17350</spage><epage>12</epage><pages>17350-12</pages><artnum>17350</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1β/TNF) stimulate miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1β (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30478292</pmid><doi>10.1038/s41598-018-35338-y</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4516-5824</orcidid><orcidid>https://orcid.org/0000-0001-8291-3468</orcidid><orcidid>https://orcid.org/0000-0001-9795-6962</orcidid><oa>free_for_read</oa></addata></record> |
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| source | SpringerOpen; Nature (Open Access); MEDLINE; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; EZB Electronic Journals Library |
| subjects | 13 14 38/109 38/77 38/89 38/90 631/250/256/2515 631/250/262/2106/2108 631/337/505 64 64/110 64/60 96 AKT protein Animal models Animals Antigens CD4 antigen Cell Line Colitis Colitis - chemically induced Colitis - genetics Colitis - immunology Colitis - pathology Colon CpG islands Dextran Dextran sulfate Epithelial cells Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelium Female Flagellin - toxicity Gastrointestinal Microbiome - genetics Homeodomain Proteins - genetics Humanities and Social Sciences Humans Immunological tolerance Inflammation Interleukin 8 Intestine Intestines - cytology Intestines - microbiology L-selectin Lipopolysaccharides Lipopolysaccharides - toxicity Lymphocytes Lymphocytes T Mice, Inbred C57BL Mice, Knockout MicroRNAs - genetics MicroRNAs - metabolism Monocyte chemoattractant protein 1 multidisciplinary MyD88 protein Myeloid Differentiation Factor 88 - genetics Myeloid Differentiation Factor 88 - metabolism NF-κB protein Peptidoglycans Rats, Wistar Rodents Science Science (multidisciplinary) Sodium TLR2 protein TLR4 protein Toll-Like Receptor 2 - genetics Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - metabolism Toll-like receptors |
| title | miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T18%3A41%3A00IST&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=miR-146a%20regulates%20the%20crosstalk%20between%20intestinal%20epithelial%20cells,%20microbial%20components%20and%20inflammatory%20stimuli&rft.jtitle=Scientific%20reports&rft.au=Anzola,%20Andrea&rft.date=2018-11-26&rft.volume=8&rft.issue=1&rft.spage=17350&rft.epage=12&rft.pages=17350-12&rft.artnum=17350&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-018-35338-y&rft_dat=%3Cproquest_pubme%3E2138064312%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=2138064312&rft_id=info:pmid/30478292&rfr_iscdi=true |