The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation In Vitro
Identifieur interne : 002360 ( Pmc/Curation ); précédent : 002359; suivant : 002361The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation In Vitro
Auteurs : Samira Khabbazi [Australie] ; Nan Xie [Australie] ; Wenjun Pu [Australie] ; Yannick Goumon [France] ; Marie-Odile Parat [Australie]Source :
- Frontiers in Pharmacology [ 1663-9812 ] ; 2016.
Abstract
Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models. A growing number of studies indicate that TLR4 can respond to opioids, including the opioid receptor-inactive morphine metabolite morphine-3-glucuronide (M3G). We measured the activation of TLR4 in a reporter cell line exogenously expressing TLR4 and TLR4 co-receptors, and confirmed that M3G weakly but significantly activates TLR4. We hypothesized that M3G would promote the expression of classical activation signature genes in macrophages
Url:
DOI: 10.3389/fphar.2016.00441
PubMed: 27909407
PubMed Central: 5112272
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation <italic>In Vitro</italic></title><author><name sortKey="Khabbazi, Samira" sort="Khabbazi, Samira" uniqKey="Khabbazi S" first="Samira" last="Khabbazi">Samira Khabbazi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Xie, Nan" sort="Xie, Nan" uniqKey="Xie N" first="Nan" last="Xie">Nan Xie</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Pu, Wenjun" sort="Pu, Wenjun" uniqKey="Pu W" first="Wenjun" last="Pu">Wenjun Pu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Goumon, Yannick" sort="Goumon, Yannick" uniqKey="Goumon Y" first="Yannick" last="Goumon">Yannick Goumon</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>CNRS UPR3212, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique–University of Strasbourg</institution><country>Strasbourg, France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Parat, Marie Odile" sort="Parat, Marie Odile" uniqKey="Parat M" first="Marie-Odile" last="Parat">Marie-Odile Parat</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27909407</idno><idno type="pmc">5112272</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112272</idno><idno type="RBID">PMC:5112272</idno><idno type="doi">10.3389/fphar.2016.00441</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002510</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002510</idno><idno type="wicri:Area/Pmc/Curation">002360</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002360</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation <italic>In Vitro</italic></title><author><name sortKey="Khabbazi, Samira" sort="Khabbazi, Samira" uniqKey="Khabbazi S" first="Samira" last="Khabbazi">Samira Khabbazi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Xie, Nan" sort="Xie, Nan" uniqKey="Xie N" first="Nan" last="Xie">Nan Xie</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Pu, Wenjun" sort="Pu, Wenjun" uniqKey="Pu W" first="Wenjun" last="Pu">Wenjun Pu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Goumon, Yannick" sort="Goumon, Yannick" uniqKey="Goumon Y" first="Yannick" last="Goumon">Yannick Goumon</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>CNRS UPR3212, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique–University of Strasbourg</institution><country>Strasbourg, France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author><author><name sortKey="Parat, Marie Odile" sort="Parat, Marie Odile" uniqKey="Parat M" first="Marie-Odile" last="Parat">Marie-Odile Parat</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Pharmacology</title><idno type="eISSN">1663-9812</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models. A growing number of studies indicate that TLR4 can respond to opioids, including the opioid receptor-inactive morphine metabolite morphine-3-glucuronide (M3G). We measured the activation of TLR4 in a reporter cell line exogenously expressing TLR4 and TLR4 co-receptors, and confirmed that M3G weakly but significantly activates TLR4. We hypothesized that M3G would promote the expression of classical activation signature genes in macrophages <italic>in vitro</italic>. We exposed mouse and human macrophage cell lines to M3G or the TLR4 activator lipopolysaccharide (LPS), alone or in combination with interferon gamma (IFN-γ). The classical macrophage activation markers tested were iNOS, CD86, IL-6, or TNF-α in RAW 264.7 cells and IL-6, IL-12, IL-23, TNF-α, CXCL10, and CXCL11 in THP1 cells. Our results show that despite exhibiting TLR4-activation ability, M3G does not elicit the expression of classical activation markers in LPS-responsive macrophages.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Afsharimani, B" uniqKey="Afsharimani B">B. Afsharimani</name></author><author><name sortKey="Baran, J" uniqKey="Baran J">J. Baran</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S. Watanabe</name></author><author><name sortKey="Lindner, D" uniqKey="Lindner D">D. Lindner</name></author><author><name sortKey="Cabot, P" uniqKey="Cabot P">P. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Front Pharmacol</journal-id><journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id><journal-title-group><journal-title>Frontiers in Pharmacology</journal-title></journal-title-group><issn pub-type="epub">1663-9812</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27909407</article-id><article-id pub-id-type="pmc">5112272</article-id><article-id pub-id-type="doi">10.3389/fphar.2016.00441</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject><subj-group><subject>Original Research</subject></subj-group></subj-group></article-categories><title-group><article-title>The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation <italic>In Vitro</italic></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Khabbazi</surname><given-names>Samira</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/241688/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Xie</surname><given-names>Nan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/390974/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Pu</surname><given-names>Wenjun</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/390975/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Goumon</surname><given-names>Yannick</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/253945/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Parat</surname><given-names>Marie-Odile</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/26634/overview"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>Pharmacy Australia Centre of Excellence, School of Pharmacy, University of Queensland, Woolloongabba</institution><country>QLD, Australia</country></aff><aff id="aff2"><sup>2</sup><institution>CNRS UPR3212, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique–University of Strasbourg</institution><country>Strasbourg, France</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: <italic>Amit K. Tiwari, University of Toledo, USA</italic></p></fn><fn fn-type="edited-by"><p>Reviewed by: <italic>Alvaro Diaz, University of the Republic, Uruguay; Wang Lingzhi, National University of Singapore, Singapore; Hemlata Sukhija, Children’s Hospital Los Angeles, USA</italic></p></fn><corresp id="fn001">*Correspondence: <italic>Marie-Odile Parat, <email xlink:type="simple">m.parat@uq.edu.au</email></italic></corresp><fn fn-type="other" id="fn002"><p>This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology</p></fn></author-notes><pub-date pub-type="epub"><day>17</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>7</volume><elocation-id>441</elocation-id><history><date date-type="received"><day>05</day><month>9</month><year>2016</year></date><date date-type="accepted"><day>04</day><month>11</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016 Khabbazi, Xie, Pu, Goumon and Parat.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Khabbazi, Xie, Pu, Goumon and Parat</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models. A growing number of studies indicate that TLR4 can respond to opioids, including the opioid receptor-inactive morphine metabolite morphine-3-glucuronide (M3G). We measured the activation of TLR4 in a reporter cell line exogenously expressing TLR4 and TLR4 co-receptors, and confirmed that M3G weakly but significantly activates TLR4. We hypothesized that M3G would promote the expression of classical activation signature genes in macrophages <italic>in vitro</italic>. We exposed mouse and human macrophage cell lines to M3G or the TLR4 activator lipopolysaccharide (LPS), alone or in combination with interferon gamma (IFN-γ). The classical macrophage activation markers tested were iNOS, CD86, IL-6, or TNF-α in RAW 264.7 cells and IL-6, IL-12, IL-23, TNF-α, CXCL10, and CXCL11 in THP1 cells. Our results show that despite exhibiting TLR4-activation ability, M3G does not elicit the expression of classical activation markers in LPS-responsive macrophages.</p></abstract><kwd-group><kwd>classically activated macrophages</kwd><kwd>tumor-associated macrophages</kwd><kwd>morphine-3-glucuronide</kwd><kwd>toll like receptor 4</kwd><kwd>lipopolysaccharide</kwd><kwd>interferon gamma</kwd><kwd>THP1</kwd><kwd>RAW267.4</kwd></kwd-group><counts><fig-count count="6"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="36"></ref-count><page-count count="9"></page-count><word-count count="0"></word-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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