Mitochondrial transcription factor A, an endogenous danger signal, promotes TNFα release via RAGE- and TLR9-responsive plasmacytoid dendritic cells
Mitochondrial transcription factor A (TFAM) is normally bound to and remains associated with mitochondrial DNA (mtDNA) when released from damaged cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched DNA), amplifies TNFα release from TLR9-expressing plasmacytoid dendritic cell...
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| description | Mitochondrial transcription factor A (TFAM) is normally bound to and remains associated with mitochondrial DNA (mtDNA) when released from damaged cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched DNA), amplifies TNFα release from TLR9-expressing plasmacytoid dendritic cells (pDCs) by engaging RAGE.
Murine Flt3 ligand-expanded splenocytes obtained from C57BL/6 mice were treated with recombinant human TFAM, alone or in combination with CpG-enriched DNA with subsequent TNFα release measured by ELISA. The role of RAGE was determined by pre-treatment with soluble RAGE or heparin or by employing matching RAGE (-/-) splenocytes. TLR9 signaling was evaluated using a specific TLR9-blocking oligonucleotide and by inhibiting endosomal processing, PI3K and NF-κB. Additional studies examined whether heparin sulfate moieties or endothelin converting enzyme-1 (ECE-1)-dependent recycling of endosomal receptors were required for TFAM and CpG DNA recognition.
TFAM augmented splenocyte TNFα release in response to CpGA DNA, which was strongly dependent upon pDCs and regulated by RAGE and TLR9 receptors. Putative TLR9 signaling pathways, including endosomal acidification and signaling through PI3K and NF-κB, were essential for splenocyte TNFα release in response to TFAM+CpGA DNA. Interestingly, TNFα release depended upon endothelin converting enzyme (ECE)-1, which cleaves and presumably activates TLR9 within endosomes. Recognition of the TFAM-CpGA DNA complex was dependent upon heparin sulfate moieties, and recombinant TFAM Box 1 and Box 2 proteins were equivalent in terms of augmenting TNFα release.
TFAM promoted TNFα release in a splenocyte culture model representing complex cell-cell interactions in vivo with pDCs playing a critical role. To our knowledge, this study is the first to incriminate ECE-1-dependent endosomal cleavage of TLR9 as a critical step in the signaling pathway leading to TNFα release. These findings, and others reported herein, significantly advance our understanding of sterile immune responses triggered by mitochondrial danger signals. |
| doi_str_mv | 10.1371/journal.pone.0072354 |
| format | Article |
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Murine Flt3 ligand-expanded splenocytes obtained from C57BL/6 mice were treated with recombinant human TFAM, alone or in combination with CpG-enriched DNA with subsequent TNFα release measured by ELISA. The role of RAGE was determined by pre-treatment with soluble RAGE or heparin or by employing matching RAGE (-/-) splenocytes. TLR9 signaling was evaluated using a specific TLR9-blocking oligonucleotide and by inhibiting endosomal processing, PI3K and NF-κB. Additional studies examined whether heparin sulfate moieties or endothelin converting enzyme-1 (ECE-1)-dependent recycling of endosomal receptors were required for TFAM and CpG DNA recognition.
TFAM augmented splenocyte TNFα release in response to CpGA DNA, which was strongly dependent upon pDCs and regulated by RAGE and TLR9 receptors. Putative TLR9 signaling pathways, including endosomal acidification and signaling through PI3K and NF-κB, were essential for splenocyte TNFα release in response to TFAM+CpGA DNA. Interestingly, TNFα release depended upon endothelin converting enzyme (ECE)-1, which cleaves and presumably activates TLR9 within endosomes. Recognition of the TFAM-CpGA DNA complex was dependent upon heparin sulfate moieties, and recombinant TFAM Box 1 and Box 2 proteins were equivalent in terms of augmenting TNFα release.
TFAM promoted TNFα release in a splenocyte culture model representing complex cell-cell interactions in vivo with pDCs playing a critical role. To our knowledge, this study is the first to incriminate ECE-1-dependent endosomal cleavage of TLR9 as a critical step in the signaling pathway leading to TNFα release. These findings, and others reported herein, significantly advance our understanding of sterile immune responses triggered by mitochondrial danger signals.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0072354</identifier><identifier>PMID: 23951313</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Acidification ; Animals ; Anticoagulants ; Cell culture ; Cell interactions ; Cell Line ; Converting ; CpG Islands ; Critical care ; Cytokines ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Deoxyribonucleic acid ; DNA ; DNA, Mitochondrial - immunology ; DNA, Mitochondrial - metabolism ; DNA-Binding Proteins - metabolism ; Endosomes ; Endothelin ; Endothelins ; Enzyme-linked immunosorbent assay ; Enzymes ; Equivalence ; FLT3L protein ; Hazards ; Heparin ; HMGB1 Protein - metabolism ; HMGB2 Protein - metabolism ; Humans ; Illnesses ; Immune response ; In vivo methods and tests ; Inflammation ; Ischemia ; Kinases ; Laboratory animals ; Male ; Mice ; Mitochondrial DNA ; Mitochondrial Proteins - metabolism ; Mitogen-Activated Protein Kinases - metabolism ; Models, Biological ; Multiple organ dysfunction syndrome ; NF-kappa B - metabolism ; NF-κB protein ; Oligonucleotides ; Phosphatidylinositol 3-Kinases - metabolism ; Pretreatment ; Protein Binding ; Proteins ; Receptors ; Recognition ; Signal Transduction ; Signaling ; Sleep ; Spleen - cytology ; Spleen - metabolism ; Splenocytes ; Sulfate ; Sulfates ; TLR9 protein ; Toll-Like Receptor 9 - metabolism ; Toll-like receptors ; Transcription factors ; Transcription Factors - metabolism ; Trauma ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Veterinary colleges ; Veterinary medicine</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e72354-e72354</ispartof><rights>2013 Julian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>2013 Julian et al 2013 Julian et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-14a27bc0b6e05c62ce024c2f379e83e225791d5336a102606299a3eedf6cfa103</citedby><cites>FETCH-LOGICAL-c526t-14a27bc0b6e05c62ce024c2f379e83e225791d5336a102606299a3eedf6cfa103</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/PMC3741150/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741150/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23951313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Fitzgerald-Bocarsly, Patricia</contributor><creatorcontrib>Julian, Mark W</creatorcontrib><creatorcontrib>Shao, Guohong</creatorcontrib><creatorcontrib>Vangundy, Zachary C</creatorcontrib><creatorcontrib>Papenfuss, Tracey L</creatorcontrib><creatorcontrib>Crouser, Elliott D</creatorcontrib><title>Mitochondrial transcription factor A, an endogenous danger signal, promotes TNFα release via RAGE- and TLR9-responsive plasmacytoid dendritic cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mitochondrial transcription factor A (TFAM) is normally bound to and remains associated with mitochondrial DNA (mtDNA) when released from damaged cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched DNA), amplifies TNFα release from TLR9-expressing plasmacytoid dendritic cells (pDCs) by engaging RAGE.
Murine Flt3 ligand-expanded splenocytes obtained from C57BL/6 mice were treated with recombinant human TFAM, alone or in combination with CpG-enriched DNA with subsequent TNFα release measured by ELISA. The role of RAGE was determined by pre-treatment with soluble RAGE or heparin or by employing matching RAGE (-/-) splenocytes. TLR9 signaling was evaluated using a specific TLR9-blocking oligonucleotide and by inhibiting endosomal processing, PI3K and NF-κB. Additional studies examined whether heparin sulfate moieties or endothelin converting enzyme-1 (ECE-1)-dependent recycling of endosomal receptors were required for TFAM and CpG DNA recognition.
TFAM augmented splenocyte TNFα release in response to CpGA DNA, which was strongly dependent upon pDCs and regulated by RAGE and TLR9 receptors. Putative TLR9 signaling pathways, including endosomal acidification and signaling through PI3K and NF-κB, were essential for splenocyte TNFα release in response to TFAM+CpGA DNA. Interestingly, TNFα release depended upon endothelin converting enzyme (ECE)-1, which cleaves and presumably activates TLR9 within endosomes. Recognition of the TFAM-CpGA DNA complex was dependent upon heparin sulfate moieties, and recombinant TFAM Box 1 and Box 2 proteins were equivalent in terms of augmenting TNFα release.
TFAM promoted TNFα release in a splenocyte culture model representing complex cell-cell interactions in vivo with pDCs playing a critical role. To our knowledge, this study is the first to incriminate ECE-1-dependent endosomal cleavage of TLR9 as a critical step in the signaling pathway leading to TNFα release. These findings, and others reported herein, significantly advance our understanding of sterile immune responses triggered by mitochondrial danger signals.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Acidification</subject><subject>Animals</subject><subject>Anticoagulants</subject><subject>Cell culture</subject><subject>Cell interactions</subject><subject>Cell Line</subject><subject>Converting</subject><subject>CpG Islands</subject><subject>Critical care</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Mitochondrial - immunology</subject><subject>DNA, Mitochondrial - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endosomes</subject><subject>Endothelin</subject><subject>Endothelins</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Equivalence</subject><subject>FLT3L protein</subject><subject>Hazards</subject><subject>Heparin</subject><subject>HMGB1 Protein - metabolism</subject><subject>HMGB2 Protein - metabolism</subject><subject>Humans</subject><subject>Illnesses</subject><subject>Immune response</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Mice</subject><subject>Mitochondrial DNA</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Models, Biological</subject><subject>Multiple organ dysfunction syndrome</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Oligonucleotides</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Pretreatment</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Recognition</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Sleep</subject><subject>Spleen - cytology</subject><subject>Spleen - metabolism</subject><subject>Splenocytes</subject><subject>Sulfate</subject><subject>Sulfates</subject><subject>TLR9 protein</subject><subject>Toll-Like Receptor 9 - metabolism</subject><subject>Toll-like receptors</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Trauma</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><subject>Veterinary colleges</subject><subject>Veterinary medicine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUttuEzEQXSEQLYE_QGCJFx66wfbsJftSKaraUimAVIVna9aeTV1t7GBvIvU_-BF-hG_CS9KqRTyNNXPOzJnxybK3gk8F1OLTrd8Gh_104x1NOa8llMWz7Fg0IPNKcnj-6H2UvYrxlvMSZlX1MjuS0JQCBBxnP7_Ywesb70yw2LMhoIs62M1gvWMd6sEHNj9h6Bg541fk_DYyg25FgUW7SgJO2Cb4tR8osuXXi9-_WKCeMBLbWWTX88vzPLENWy6umzxQTHKj3RHb9BjXqO8Gbw0zNM4frGaa-j6-zl502Ed6c4iT7PvF-fLsc774dnl1Nl_kupTVkIsCZd1q3lbES11JTVwWWnZQNzQDkrKsG2FKgAoFlxWvZNMgEJmu0l1KwSR7v--76X1Uh4NGJQrgheSzBhLiao8wHm_VJtg1hjvl0aq_CR9WCkPS3ZNCI2stuahnLRVYzNAAoYAWZMuBpzjJTg_Ttu2ajCaXrt0_afq04uyNWvmdgroQohzlfjw0CP7HluKg1jaOB0NH6VuS7rQkb0oYoR_-gf5_u2KP0sHHGKh7ECO4Gk12z1KjydTBZIn27vEiD6R7V8Ef1dPSEQ</recordid><startdate>20130812</startdate><enddate>20130812</enddate><creator>Julian, Mark W</creator><creator>Shao, Guohong</creator><creator>Vangundy, Zachary C</creator><creator>Papenfuss, Tracey L</creator><creator>Crouser, Elliott D</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>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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130812</creationdate><title>Mitochondrial transcription factor A, an endogenous danger signal, promotes TNFα release via RAGE- and TLR9-responsive plasmacytoid dendritic cells</title><author>Julian, Mark W ; Shao, Guohong ; Vangundy, Zachary C ; Papenfuss, Tracey L ; Crouser, Elliott D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-14a27bc0b6e05c62ce024c2f379e83e225791d5336a102606299a3eedf6cfa103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Acidification</topic><topic>Animals</topic><topic>Anticoagulants</topic><topic>Cell culture</topic><topic>Cell interactions</topic><topic>Cell Line</topic><topic>Converting</topic><topic>CpG Islands</topic><topic>Critical care</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Mitochondrial - immunology</topic><topic>DNA, Mitochondrial - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Endosomes</topic><topic>Endothelin</topic><topic>Endothelins</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Enzymes</topic><topic>Equivalence</topic><topic>FLT3L protein</topic><topic>Hazards</topic><topic>Heparin</topic><topic>HMGB1 Protein - metabolism</topic><topic>HMGB2 Protein - metabolism</topic><topic>Humans</topic><topic>Illnesses</topic><topic>Immune response</topic><topic>In vivo methods and tests</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Mice</topic><topic>Mitochondrial DNA</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Models, Biological</topic><topic>Multiple organ dysfunction syndrome</topic><topic>NF-kappa B - 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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>Julian, Mark W</au><au>Shao, Guohong</au><au>Vangundy, Zachary C</au><au>Papenfuss, Tracey L</au><au>Crouser, Elliott D</au><au>Fitzgerald-Bocarsly, Patricia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial transcription factor A, an endogenous danger signal, promotes TNFα release via RAGE- and TLR9-responsive plasmacytoid dendritic cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-12</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e72354</spage><epage>e72354</epage><pages>e72354-e72354</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Mitochondrial transcription factor A (TFAM) is normally bound to and remains associated with mitochondrial DNA (mtDNA) when released from damaged cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched DNA), amplifies TNFα release from TLR9-expressing plasmacytoid dendritic cells (pDCs) by engaging RAGE.
Murine Flt3 ligand-expanded splenocytes obtained from C57BL/6 mice were treated with recombinant human TFAM, alone or in combination with CpG-enriched DNA with subsequent TNFα release measured by ELISA. The role of RAGE was determined by pre-treatment with soluble RAGE or heparin or by employing matching RAGE (-/-) splenocytes. TLR9 signaling was evaluated using a specific TLR9-blocking oligonucleotide and by inhibiting endosomal processing, PI3K and NF-κB. Additional studies examined whether heparin sulfate moieties or endothelin converting enzyme-1 (ECE-1)-dependent recycling of endosomal receptors were required for TFAM and CpG DNA recognition.
TFAM augmented splenocyte TNFα release in response to CpGA DNA, which was strongly dependent upon pDCs and regulated by RAGE and TLR9 receptors. Putative TLR9 signaling pathways, including endosomal acidification and signaling through PI3K and NF-κB, were essential for splenocyte TNFα release in response to TFAM+CpGA DNA. Interestingly, TNFα release depended upon endothelin converting enzyme (ECE)-1, which cleaves and presumably activates TLR9 within endosomes. Recognition of the TFAM-CpGA DNA complex was dependent upon heparin sulfate moieties, and recombinant TFAM Box 1 and Box 2 proteins were equivalent in terms of augmenting TNFα release.
TFAM promoted TNFα release in a splenocyte culture model representing complex cell-cell interactions in vivo with pDCs playing a critical role. To our knowledge, this study is the first to incriminate ECE-1-dependent endosomal cleavage of TLR9 as a critical step in the signaling pathway leading to TNFα release. These findings, and others reported herein, significantly advance our understanding of sterile immune responses triggered by mitochondrial danger signals.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23951313</pmid><doi>10.1371/journal.pone.0072354</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-08, Vol.8 (8), p.e72354-e72354 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1430420893 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Acidification Animals Anticoagulants Cell culture Cell interactions Cell Line Converting CpG Islands Critical care Cytokines Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism Deoxyribonucleic acid DNA DNA, Mitochondrial - immunology DNA, Mitochondrial - metabolism DNA-Binding Proteins - metabolism Endosomes Endothelin Endothelins Enzyme-linked immunosorbent assay Enzymes Equivalence FLT3L protein Hazards Heparin HMGB1 Protein - metabolism HMGB2 Protein - metabolism Humans Illnesses Immune response In vivo methods and tests Inflammation Ischemia Kinases Laboratory animals Male Mice Mitochondrial DNA Mitochondrial Proteins - metabolism Mitogen-Activated Protein Kinases - metabolism Models, Biological Multiple organ dysfunction syndrome NF-kappa B - metabolism NF-κB protein Oligonucleotides Phosphatidylinositol 3-Kinases - metabolism Pretreatment Protein Binding Proteins Receptors Recognition Signal Transduction Signaling Sleep Spleen - cytology Spleen - metabolism Splenocytes Sulfate Sulfates TLR9 protein Toll-Like Receptor 9 - metabolism Toll-like receptors Transcription factors Transcription Factors - metabolism Trauma Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Veterinary colleges Veterinary medicine |
| title | Mitochondrial transcription factor A, an endogenous danger signal, promotes TNFα release via RAGE- and TLR9-responsive plasmacytoid dendritic cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T17%3A57%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitochondrial%20transcription%20factor%20A,%20an%20endogenous%20danger%20signal,%20promotes%20TNF%CE%B1%20release%20via%20RAGE-%20and%20TLR9-responsive%20plasmacytoid%20dendritic%20cells&rft.jtitle=PloS%20one&rft.au=Julian,%20Mark%20W&rft.date=2013-08-12&rft.volume=8&rft.issue=8&rft.spage=e72354&rft.epage=e72354&rft.pages=e72354-e72354&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0072354&rft_dat=%3Cproquest_plos_%3E1426009530%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1430420893&rft_id=info:pmid/23951313&rft_doaj_id=oai_doaj_org_article_ad27c20178be4a48ad3ea13b32b0303b&rfr_iscdi=true |