mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages
Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro- and anti-inflammatory cytokines that are induced by extrinsic antigens, but the function of mTORC1 in flagellin-induced inflammatory response...
Gespeichert in:
Veröffentlicht in: | PloS one 2015-05, Vol.10 (5), p.e0125910-e0125910 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e0125910 |
---|---|
container_issue | 5 |
container_start_page | e0125910 |
container_title | PloS one |
container_volume | 10 |
creator | Bao, Wenlei Wang, Yanfeng Fu, Yuting Jia, Xiaoyang Li, Jiaxin Vangan, Nyamtsengel Bao, Lili Hao, Huifang Wang, Zhigang |
description | Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro- and anti-inflammatory cytokines that are induced by extrinsic antigens, but the function of mTORC1 in flagellin-induced inflammatory response is unknown. The purpose of this study was to examine the role and the mechanism of PI3K/Akt/mTOR pathway in flagellin-induced cytokine expression in mouse macrophages. We observed that flagellin upregulated TNF-α time- and dose-dependently. Flagellin stimulated rapid ( |
doi_str_mv | 10.1371/journal.pone.0125910 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1678772071</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A430193547</galeid><doaj_id>oai_doaj_org_article_9404b1763c0e4d8e97beff5543b9866d</doaj_id><sourcerecordid>A430193547</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-3ff8afe469247317bcae24e8ca88d4bc8853b4b4ab2a46e2852c038948587b993</originalsourceid><addsrcrecordid>eNqNkl9v0zAUxSMEYqPwDRBUQkLw0OJ_iZ0XpKliI9JQpTJ4tRznJk3lxF2cIPbtuaXZ1KA9oDw4tn_3XPv4RNFrSpaUS_pp54euNW659y0sCWVxSsmT6JymnC0SRvjTk_-z6EUIO0JirpLkeXSGsGCEyPPoqrlZb1Z0voFqcKaHML90pgLn6naRtcVgoZhnbelM05jed3cIBuwYYF6382_Gdn6_RT68jJ6VxgV4NY6z6Mfll5vV18X1-ipbXVwvbJKyfsHLUpkSBE6E5FTm1gAToKxRqhC5VSrmuciFyZkRCTAVM0u4SoWKlczTlM-it0fdvfNBjx4ETROppGREUiSyI1F4s9P7rm5Md6e9qfXfBd9V2nR9bR3oVBCRU5lwS0AUClKZQ1nGseB5ikYVqPV57DbkDRQW2r4zbiI63Wnrra78Ly3QXpEkKPBhFOj87QCh100dLNprWvDD4dyKUCU5Y4i--wd9_HYjVRm8QN2WHvvag6i-EJzgi8do7CxaPkLhV0BTWwxMWeP6pODjpACZHn73lRlC0Nn3zf-z659T9v0JuwXj-m3wbuhrzNAUFEcQExVCB-WDyZToQ97v3dCHvOsx71j25vSBHoruA87_AFlt-M8</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1678772071</pqid></control><display><type>article</type><title>mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Bao, Wenlei ; Wang, Yanfeng ; Fu, Yuting ; Jia, Xiaoyang ; Li, Jiaxin ; Vangan, Nyamtsengel ; Bao, Lili ; Hao, Huifang ; Wang, Zhigang</creator><contributor>Cheng, Jin Q.</contributor><creatorcontrib>Bao, Wenlei ; Wang, Yanfeng ; Fu, Yuting ; Jia, Xiaoyang ; Li, Jiaxin ; Vangan, Nyamtsengel ; Bao, Lili ; Hao, Huifang ; Wang, Zhigang ; Cheng, Jin Q.</creatorcontrib><description>Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro- and anti-inflammatory cytokines that are induced by extrinsic antigens, but the function of mTORC1 in flagellin-induced inflammatory response is unknown. The purpose of this study was to examine the role and the mechanism of PI3K/Akt/mTOR pathway in flagellin-induced cytokine expression in mouse macrophages. We observed that flagellin upregulated TNF-α time- and dose-dependently. Flagellin stimulated rapid (<15 min) PI3K/Akt/mTOR phosphorylation that was mediated by TLR5. Inhibition of PI3K with LY294002 and wortmannin, and of mTORC1 with rapamycin decreased flagellin-induced TNF-α and IL-6 expression and cell proliferation. The activation of NF-κB p65 and STAT3 was regulated by mTORC1 via degradation of IκBα and phosphorylation of STAT3 in response to flagellin, respectively. Thus, the PI3K/Akt/mTORC1 pathway regulates the innate immune response to bacterial flagellin. Rapamycin is potential therapy that can regulate host defense against pathogenic infections.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0125910</identifier><identifier>PMID: 25942007</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Animals ; Antigens ; Apoptosis ; Bacteria ; Bacterial proteins ; Biodegradation ; Cancer ; Cell activation ; Cell culture ; Cell growth ; Cell Line ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Survival ; Cellular control mechanisms ; Cellular signal transduction ; Chromones - pharmacology ; Cytokines ; Cytokines - metabolism ; Dose-Response Relationship, Drug ; Flagellin ; Flagellin - metabolism ; Flagellin - pharmacology ; Gene expression ; Gene Expression Regulation ; Health aspects ; Immune response ; Immune system ; Immunoglobulins ; Inflammation ; Inflammation - genetics ; Inflammation - immunology ; Inflammation - metabolism ; Inflammatory response ; Innate immunity ; Interleukin 6 ; Kinases ; Life sciences ; Macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages, Peritoneal - drug effects ; Macrophages, Peritoneal - immunology ; Macrophages, Peritoneal - metabolism ; Mammals ; MAP Kinase Signaling System - drug effects ; Mechanistic Target of Rapamycin Complex 1 ; Metabolism ; Mice ; Morpholines - pharmacology ; Multiprotein Complexes - metabolism ; NF-kappa B - metabolism ; NF-κB protein ; Pattern recognition ; Penicillin ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphorylation ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Rapamycin ; Signal Transduction - drug effects ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; TLR5 protein ; Toll-Like Receptor 5 - antagonists & inhibitors ; Toll-Like Receptor 5 - metabolism ; Toll-like receptors ; TOR protein ; TOR Serine-Threonine Kinases - metabolism ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Viral infections ; Wortmannin</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0125910-e0125910</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Bao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Bao et al 2015 Bao et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-3ff8afe469247317bcae24e8ca88d4bc8853b4b4ab2a46e2852c038948587b993</citedby><cites>FETCH-LOGICAL-c692t-3ff8afe469247317bcae24e8ca88d4bc8853b4b4ab2a46e2852c038948587b993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420466/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420466/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25942007$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cheng, Jin Q.</contributor><creatorcontrib>Bao, Wenlei</creatorcontrib><creatorcontrib>Wang, Yanfeng</creatorcontrib><creatorcontrib>Fu, Yuting</creatorcontrib><creatorcontrib>Jia, Xiaoyang</creatorcontrib><creatorcontrib>Li, Jiaxin</creatorcontrib><creatorcontrib>Vangan, Nyamtsengel</creatorcontrib><creatorcontrib>Bao, Lili</creatorcontrib><creatorcontrib>Hao, Huifang</creatorcontrib><creatorcontrib>Wang, Zhigang</creatorcontrib><title>mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro- and anti-inflammatory cytokines that are induced by extrinsic antigens, but the function of mTORC1 in flagellin-induced inflammatory response is unknown. The purpose of this study was to examine the role and the mechanism of PI3K/Akt/mTOR pathway in flagellin-induced cytokine expression in mouse macrophages. We observed that flagellin upregulated TNF-α time- and dose-dependently. Flagellin stimulated rapid (<15 min) PI3K/Akt/mTOR phosphorylation that was mediated by TLR5. Inhibition of PI3K with LY294002 and wortmannin, and of mTORC1 with rapamycin decreased flagellin-induced TNF-α and IL-6 expression and cell proliferation. The activation of NF-κB p65 and STAT3 was regulated by mTORC1 via degradation of IκBα and phosphorylation of STAT3 in response to flagellin, respectively. Thus, the PI3K/Akt/mTORC1 pathway regulates the innate immune response to bacterial flagellin. Rapamycin is potential therapy that can regulate host defense against pathogenic infections.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Bacteria</subject><subject>Bacterial proteins</subject><subject>Biodegradation</subject><subject>Cancer</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival</subject><subject>Cellular control mechanisms</subject><subject>Cellular signal transduction</subject><subject>Chromones - pharmacology</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Flagellin</subject><subject>Flagellin - metabolism</subject><subject>Flagellin - pharmacology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Health aspects</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunoglobulins</subject><subject>Inflammation</subject><subject>Inflammation - genetics</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory response</subject><subject>Innate immunity</subject><subject>Interleukin 6</subject><subject>Kinases</subject><subject>Life sciences</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages, Peritoneal - drug effects</subject><subject>Macrophages, Peritoneal - immunology</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>Mammals</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mechanistic Target of Rapamycin Complex 1</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Morpholines - pharmacology</subject><subject>Multiprotein Complexes - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Pattern recognition</subject><subject>Penicillin</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rapamycin</subject><subject>Signal Transduction - drug effects</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>TLR5 protein</subject><subject>Toll-Like Receptor 5 - antagonists & inhibitors</subject><subject>Toll-Like Receptor 5 - metabolism</subject><subject>Toll-like receptors</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><subject>Viral infections</subject><subject>Wortmannin</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl9v0zAUxSMEYqPwDRBUQkLw0OJ_iZ0XpKliI9JQpTJ4tRznJk3lxF2cIPbtuaXZ1KA9oDw4tn_3XPv4RNFrSpaUS_pp54euNW659y0sCWVxSsmT6JymnC0SRvjTk_-z6EUIO0JirpLkeXSGsGCEyPPoqrlZb1Z0voFqcKaHML90pgLn6naRtcVgoZhnbelM05jed3cIBuwYYF6382_Gdn6_RT68jJ6VxgV4NY6z6Mfll5vV18X1-ipbXVwvbJKyfsHLUpkSBE6E5FTm1gAToKxRqhC5VSrmuciFyZkRCTAVM0u4SoWKlczTlM-it0fdvfNBjx4ETROppGREUiSyI1F4s9P7rm5Md6e9qfXfBd9V2nR9bR3oVBCRU5lwS0AUClKZQ1nGseB5ikYVqPV57DbkDRQW2r4zbiI63Wnrra78Ly3QXpEkKPBhFOj87QCh100dLNprWvDD4dyKUCU5Y4i--wd9_HYjVRm8QN2WHvvag6i-EJzgi8do7CxaPkLhV0BTWwxMWeP6pODjpACZHn73lRlC0Nn3zf-z659T9v0JuwXj-m3wbuhrzNAUFEcQExVCB-WDyZToQ97v3dCHvOsx71j25vSBHoruA87_AFlt-M8</recordid><startdate>20150505</startdate><enddate>20150505</enddate><creator>Bao, Wenlei</creator><creator>Wang, Yanfeng</creator><creator>Fu, Yuting</creator><creator>Jia, Xiaoyang</creator><creator>Li, Jiaxin</creator><creator>Vangan, Nyamtsengel</creator><creator>Bao, Lili</creator><creator>Hao, Huifang</creator><creator>Wang, Zhigang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150505</creationdate><title>mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages</title><author>Bao, Wenlei ; Wang, Yanfeng ; Fu, Yuting ; Jia, Xiaoyang ; Li, Jiaxin ; Vangan, Nyamtsengel ; Bao, Lili ; Hao, Huifang ; Wang, Zhigang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-3ff8afe469247317bcae24e8ca88d4bc8853b4b4ab2a46e2852c038948587b993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>Bacteria</topic><topic>Bacterial proteins</topic><topic>Biodegradation</topic><topic>Cancer</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival</topic><topic>Cellular control mechanisms</topic><topic>Cellular signal transduction</topic><topic>Chromones - pharmacology</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Flagellin</topic><topic>Flagellin - metabolism</topic><topic>Flagellin - pharmacology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Health aspects</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunoglobulins</topic><topic>Inflammation</topic><topic>Inflammation - genetics</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Inflammatory response</topic><topic>Innate immunity</topic><topic>Interleukin 6</topic><topic>Kinases</topic><topic>Life sciences</topic><topic>Macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Macrophages, Peritoneal - drug effects</topic><topic>Macrophages, Peritoneal - immunology</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>Mammals</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mechanistic Target of Rapamycin Complex 1</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Morpholines - pharmacology</topic><topic>Multiprotein Complexes - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Pattern recognition</topic><topic>Penicillin</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rapamycin</topic><topic>Signal Transduction - drug effects</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>TLR5 protein</topic><topic>Toll-Like Receptor 5 - antagonists & inhibitors</topic><topic>Toll-Like Receptor 5 - metabolism</topic><topic>Toll-like receptors</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><topic>Viral infections</topic><topic>Wortmannin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bao, Wenlei</creatorcontrib><creatorcontrib>Wang, Yanfeng</creatorcontrib><creatorcontrib>Fu, Yuting</creatorcontrib><creatorcontrib>Jia, Xiaoyang</creatorcontrib><creatorcontrib>Li, Jiaxin</creatorcontrib><creatorcontrib>Vangan, Nyamtsengel</creatorcontrib><creatorcontrib>Bao, Lili</creatorcontrib><creatorcontrib>Hao, Huifang</creatorcontrib><creatorcontrib>Wang, Zhigang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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 China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bao, Wenlei</au><au>Wang, Yanfeng</au><au>Fu, Yuting</au><au>Jia, Xiaoyang</au><au>Li, Jiaxin</au><au>Vangan, Nyamtsengel</au><au>Bao, Lili</au><au>Hao, Huifang</au><au>Wang, Zhigang</au><au>Cheng, Jin Q.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-05</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0125910</spage><epage>e0125910</epage><pages>e0125910-e0125910</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro- and anti-inflammatory cytokines that are induced by extrinsic antigens, but the function of mTORC1 in flagellin-induced inflammatory response is unknown. The purpose of this study was to examine the role and the mechanism of PI3K/Akt/mTOR pathway in flagellin-induced cytokine expression in mouse macrophages. We observed that flagellin upregulated TNF-α time- and dose-dependently. Flagellin stimulated rapid (<15 min) PI3K/Akt/mTOR phosphorylation that was mediated by TLR5. Inhibition of PI3K with LY294002 and wortmannin, and of mTORC1 with rapamycin decreased flagellin-induced TNF-α and IL-6 expression and cell proliferation. The activation of NF-κB p65 and STAT3 was regulated by mTORC1 via degradation of IκBα and phosphorylation of STAT3 in response to flagellin, respectively. Thus, the PI3K/Akt/mTORC1 pathway regulates the innate immune response to bacterial flagellin. Rapamycin is potential therapy that can regulate host defense against pathogenic infections.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25942007</pmid><doi>10.1371/journal.pone.0125910</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-05, Vol.10 (5), p.e0125910-e0125910 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1678772071 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | 1-Phosphatidylinositol 3-kinase AKT protein Animals Antigens Apoptosis Bacteria Bacterial proteins Biodegradation Cancer Cell activation Cell culture Cell growth Cell Line Cell proliferation Cell Proliferation - drug effects Cell Survival Cellular control mechanisms Cellular signal transduction Chromones - pharmacology Cytokines Cytokines - metabolism Dose-Response Relationship, Drug Flagellin Flagellin - metabolism Flagellin - pharmacology Gene expression Gene Expression Regulation Health aspects Immune response Immune system Immunoglobulins Inflammation Inflammation - genetics Inflammation - immunology Inflammation - metabolism Inflammatory response Innate immunity Interleukin 6 Kinases Life sciences Macrophages Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - immunology Macrophages, Peritoneal - metabolism Mammals MAP Kinase Signaling System - drug effects Mechanistic Target of Rapamycin Complex 1 Metabolism Mice Morpholines - pharmacology Multiprotein Complexes - metabolism NF-kappa B - metabolism NF-κB protein Pattern recognition Penicillin Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphorylation Proteins Proto-Oncogene Proteins c-akt - metabolism Rapamycin Signal Transduction - drug effects Stat3 protein STAT3 Transcription Factor - metabolism TLR5 protein Toll-Like Receptor 5 - antagonists & inhibitors Toll-Like Receptor 5 - metabolism Toll-like receptors TOR protein TOR Serine-Threonine Kinases - metabolism Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Viral infections Wortmannin |
title | mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T00%3A09%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=mTORC1%20Regulates%20Flagellin-Induced%20Inflammatory%20Response%20in%20Macrophages&rft.jtitle=PloS%20one&rft.au=Bao,%20Wenlei&rft.date=2015-05-05&rft.volume=10&rft.issue=5&rft.spage=e0125910&rft.epage=e0125910&rft.pages=e0125910-e0125910&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0125910&rft_dat=%3Cgale_plos_%3EA430193547%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1678772071&rft_id=info:pmid/25942007&rft_galeid=A430193547&rft_doaj_id=oai_doaj_org_article_9404b1763c0e4d8e97beff5543b9866d&rfr_iscdi=true |