MyD88-dependent and -independent signalling via TLR3 and TLR4 are differentially modulated by Δ9-tetrahydrocannabinol and cannabidiol in human macrophages.
Identifieur interne : 000105 ( Main/Exploration ); précédent : 000104; suivant : 000106MyD88-dependent and -independent signalling via TLR3 and TLR4 are differentially modulated by Δ9-tetrahydrocannabinol and cannabidiol in human macrophages.
Auteurs : John-Mark Fitzpatrick [Irlande (pays)] ; Eleanor Minogue [Irlande (pays)] ; Lucy Curham [Irlande (pays)] ; Harry Tyrrell [Irlande (pays)] ; Philip Gavigan [Irlande (pays)] ; William Hind [Royaume-Uni] ; Eric J. Downer [Irlande (pays)]Source :
- Journal of neuroimmunology [ 1872-8421 ] ; 2020.
Descripteurs français
- KwdFr :
- Cannabidiol (pharmacologie), Dronabinol (pharmacologie), Facteur de différenciation myéloïde-88 (effets des médicaments et des substances chimiques), Facteur de différenciation myéloïde-88 (immunologie), Facteur de différenciation myéloïde-88 (métabolisme), Humains (MeSH), Inflammation (immunologie), Inflammation (métabolisme), Lignée cellulaire (MeSH), Macrophages (effets des médicaments et des substances chimiques), Macrophages (immunologie), Macrophages (métabolisme), Récepteur de type Toll-3 (effets des médicaments et des substances chimiques), Récepteur de type Toll-3 (immunologie), Récepteur de type Toll-3 (métabolisme), Récepteur de type Toll-4 (effets des médicaments et des substances chimiques), Récepteur de type Toll-4 (immunologie), Récepteur de type Toll-4 (métabolisme), Transduction du signal (effets des médicaments et des substances chimiques), Transduction du signal (immunologie).
- MESH :
- effets des médicaments et des substances chimiques : Facteur de différenciation myéloïde-88, Macrophages, Récepteur de type Toll-3, Récepteur de type Toll-4, Transduction du signal.
- immunologie : Facteur de différenciation myéloïde-88, Inflammation, Macrophages, Récepteur de type Toll-3, Récepteur de type Toll-4, Transduction du signal.
- métabolisme : Facteur de différenciation myéloïde-88, Inflammation, Macrophages, Récepteur de type Toll-3, Récepteur de type Toll-4.
- pharmacologie : Cannabidiol, Dronabinol.
- Humains, Lignée cellulaire.
English descriptors
- KwdEn :
- Cannabidiol (pharmacology), Cell Line (MeSH), Dronabinol (pharmacology), Humans (MeSH), Inflammation (immunology), Inflammation (metabolism), Macrophages (drug effects), Macrophages (immunology), Macrophages (metabolism), Myeloid Differentiation Factor 88 (drug effects), Myeloid Differentiation Factor 88 (immunology), Myeloid Differentiation Factor 88 (metabolism), Signal Transduction (drug effects), Signal Transduction (immunology), Toll-Like Receptor 3 (drug effects), Toll-Like Receptor 3 (immunology), Toll-Like Receptor 3 (metabolism), Toll-Like Receptor 4 (drug effects), Toll-Like Receptor 4 (immunology), Toll-Like Receptor 4 (metabolism).
- MESH :
- chemical , drug effects : Myeloid Differentiation Factor 88, Toll-Like Receptor 3, Toll-Like Receptor 4.
- chemical , immunology : Myeloid Differentiation Factor 88, Toll-Like Receptor 3, Toll-Like Receptor 4.
- chemical , metabolism : Myeloid Differentiation Factor 88, Toll-Like Receptor 3, Toll-Like Receptor 4.
- chemical , pharmacology : Cannabidiol, Dronabinol.
- drug effects : Macrophages, Signal Transduction.
- immunology : Inflammation, Macrophages, Signal Transduction.
- metabolism : Inflammation, Macrophages.
- Cell Line, Humans.
Abstract
Toll-like receptors (TLRs) are sensors of pathogen-associated molecules that trigger inflammatory signalling in innate immune cells including macrophages. All TLRs, with the exception of TLR3, promote intracellular signalling via recruitment of the myeloid differentiation factor 88 (MyD88) adaptor, while TLR3 signals via Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor-inducing interferon (IFN)-β (TRIF) adaptor to induce MyD88-independent signalling. Furthermore, TLR4 can activate both MyD88-dependent and -independent signalling (via TRIF). The study aim was to decipher the impact of the highly purified plant-derived (phyto) cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), when delivered in isolation and in combination (1:1), on MyD88-dependent and -independent signalling in macrophages. We employed the use of the viral dsRNA mimetic poly(I:C) and endotoxin lipopolysaccharide (LPS), to induce viral TLR3 and bacterial TLR4 signalling in human Tamm-Horsfall protein-1 (THP-1)-derived macrophages, respectively. TLR3/TLR4 stimulation promoted the activation of interferon (IFN) regulatory factor 3 (IRF3) and TLR4 promoted the activation of nuclear factor (NF)-κB signalling, with downstream production of the type I IFN-β, the chemokines CXCL10 and CXCL8, and cytokine TNF-α. THC and CBD (both at 10 μM) attenuated TLR3/4-induced IRF3 activation and induction of CXCL10/IFN-β, while both phytocannabinoids failed to impact TLR4-induced IκB-α degradation and TNF-α/CXCL8 expression. The role of CB1, CB2 and PPARγ receptors in mediating the effect of THC and CBD on MyD88-independent signalling was investigated. TLRs are attractive therapeutic targets given their role in inflammation and initiation of adaptive immunity, and data herein indicate that both CBD and THC preferentially modulate TLR3 and TLR4 signalling via MyD88-independent mechanisms in macrophages. This offers mechanistic insight into the role of phytocannabinoids in modulating cellular inflammation.
DOI: 10.1016/j.jneuroim.2020.577217
PubMed: 32244040
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Downer</name><affiliation wicri:level="1"><nlm:affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland. Electronic address: edowner@tcd.ie.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of neuroimmunology</title><idno type="eISSN">1872-8421</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cannabidiol (pharmacology)</term><term>Cell Line (MeSH)</term><term>Dronabinol (pharmacology)</term><term>Humans (MeSH)</term><term>Inflammation (immunology)</term><term>Inflammation (metabolism)</term><term>Macrophages (drug effects)</term><term>Macrophages (immunology)</term><term>Macrophages (metabolism)</term><term>Myeloid Differentiation Factor 88 (drug effects)</term><term>Myeloid Differentiation Factor 88 (immunology)</term><term>Myeloid Differentiation Factor 88 (metabolism)</term><term>Signal Transduction (drug effects)</term><term>Signal Transduction (immunology)</term><term>Toll-Like Receptor 3 (drug effects)</term><term>Toll-Like Receptor 3 (immunology)</term><term>Toll-Like Receptor 3 (metabolism)</term><term>Toll-Like Receptor 4 (drug effects)</term><term>Toll-Like Receptor 4 (immunology)</term><term>Toll-Like Receptor 4 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cannabidiol (pharmacologie)</term><term>Dronabinol (pharmacologie)</term><term>Facteur de différenciation myéloïde-88 (effets des médicaments et des substances chimiques)</term><term>Facteur de différenciation myéloïde-88 (immunologie)</term><term>Facteur de différenciation myéloïde-88 (métabolisme)</term><term>Humains (MeSH)</term><term>Inflammation (immunologie)</term><term>Inflammation (métabolisme)</term><term>Lignée cellulaire (MeSH)</term><term>Macrophages (effets des médicaments et des substances chimiques)</term><term>Macrophages (immunologie)</term><term>Macrophages (métabolisme)</term><term>Récepteur de type Toll-3 (effets des médicaments et des substances chimiques)</term><term>Récepteur de type Toll-3 (immunologie)</term><term>Récepteur de type Toll-3 (métabolisme)</term><term>Récepteur de type Toll-4 (effets des médicaments et des substances chimiques)</term><term>Récepteur de type Toll-4 (immunologie)</term><term>Récepteur de type Toll-4 (métabolisme)</term><term>Transduction du signal (effets des médicaments et des substances chimiques)</term><term>Transduction du signal (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Myeloid Differentiation Factor 88</term><term>Toll-Like Receptor 3</term><term>Toll-Like Receptor 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Myeloid Differentiation Factor 88</term><term>Toll-Like Receptor 3</term><term>Toll-Like Receptor 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Myeloid Differentiation Factor 88</term><term>Toll-Like Receptor 3</term><term>Toll-Like Receptor 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Cannabidiol</term><term>Dronabinol</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Macrophages</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Facteur de différenciation myéloïde-88</term><term>Macrophages</term><term>Récepteur de type Toll-3</term><term>Récepteur de type Toll-4</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Facteur de différenciation myéloïde-88</term><term>Inflammation</term><term>Macrophages</term><term>Récepteur de type Toll-3</term><term>Récepteur de type Toll-4</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Inflammation</term><term>Macrophages</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Inflammation</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de différenciation myéloïde-88</term><term>Inflammation</term><term>Macrophages</term><term>Récepteur de type Toll-3</term><term>Récepteur de type Toll-4</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Cannabidiol</term><term>Dronabinol</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Lignée cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Toll-like receptors (TLRs) are sensors of pathogen-associated molecules that trigger inflammatory signalling in innate immune cells including macrophages. All TLRs, with the exception of TLR3, promote intracellular signalling via recruitment of the myeloid differentiation factor 88 (MyD88) adaptor, while TLR3 signals via Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor-inducing interferon (IFN)-β (TRIF) adaptor to induce MyD88-independent signalling. Furthermore, TLR4 can activate both MyD88-dependent and -independent signalling (via TRIF). The study aim was to decipher the impact of the highly purified plant-derived (phyto) cannabinoids Δ<sup>9</sup>-tetrahydrocannabinol (THC) and cannabidiol (CBD), when delivered in isolation and in combination (1:1), on MyD88-dependent and -independent signalling in macrophages. We employed the use of the viral dsRNA mimetic poly(I:C) and endotoxin lipopolysaccharide (LPS), to induce viral TLR3 and bacterial TLR4 signalling in human Tamm-Horsfall protein-1 (THP-1)-derived macrophages, respectively. TLR3/TLR4 stimulation promoted the activation of interferon (IFN) regulatory factor 3 (IRF3) and TLR4 promoted the activation of nuclear factor (NF)-κB signalling, with downstream production of the type I IFN-β, the chemokines CXCL10 and CXCL8, and cytokine TNF-α. THC and CBD (both at 10 μM) attenuated TLR3/4-induced IRF3 activation and induction of CXCL10/IFN-β, while both phytocannabinoids failed to impact TLR4-induced IκB-α degradation and TNF-α/CXCL8 expression. The role of CB<sub>1</sub>, CB<sub>2</sub> and PPARγ receptors in mediating the effect of THC and CBD on MyD88-independent signalling was investigated. TLRs are attractive therapeutic targets given their role in inflammation and initiation of adaptive immunity, and data herein indicate that both CBD and THC preferentially modulate TLR3 and TLR4 signalling via MyD88-independent mechanisms in macrophages. This offers mechanistic insight into the role of phytocannabinoids in modulating cellular inflammation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32244040</PMID><DateCompleted><Year>2020</Year><Month>11</Month><Day>09</Day></DateCompleted><DateRevised><Year>2020</Year><Month>11</Month><Day>09</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1872-8421</ISSN><JournalIssue CitedMedium="Internet"><Volume>343</Volume><PubDate><Year>2020</Year><Month>06</Month><Day>15</Day></PubDate></JournalIssue><Title>Journal of neuroimmunology</Title><ISOAbbreviation>J Neuroimmunol</ISOAbbreviation></Journal><ArticleTitle>MyD88-dependent and -independent signalling via TLR3 and TLR4 are differentially modulated by Δ<sup>9</sup>-tetrahydrocannabinol and cannabidiol in human macrophages.</ArticleTitle><Pagination><MedlinePgn>577217</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0165-5728(20)30057-6</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jneuroim.2020.577217</ELocationID><Abstract><AbstractText>Toll-like receptors (TLRs) are sensors of pathogen-associated molecules that trigger inflammatory signalling in innate immune cells including macrophages. All TLRs, with the exception of TLR3, promote intracellular signalling via recruitment of the myeloid differentiation factor 88 (MyD88) adaptor, while TLR3 signals via Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor-inducing interferon (IFN)-β (TRIF) adaptor to induce MyD88-independent signalling. Furthermore, TLR4 can activate both MyD88-dependent and -independent signalling (via TRIF). The study aim was to decipher the impact of the highly purified plant-derived (phyto) cannabinoids Δ<sup>9</sup>-tetrahydrocannabinol (THC) and cannabidiol (CBD), when delivered in isolation and in combination (1:1), on MyD88-dependent and -independent signalling in macrophages. We employed the use of the viral dsRNA mimetic poly(I:C) and endotoxin lipopolysaccharide (LPS), to induce viral TLR3 and bacterial TLR4 signalling in human Tamm-Horsfall protein-1 (THP-1)-derived macrophages, respectively. TLR3/TLR4 stimulation promoted the activation of interferon (IFN) regulatory factor 3 (IRF3) and TLR4 promoted the activation of nuclear factor (NF)-κB signalling, with downstream production of the type I IFN-β, the chemokines CXCL10 and CXCL8, and cytokine TNF-α. THC and CBD (both at 10 μM) attenuated TLR3/4-induced IRF3 activation and induction of CXCL10/IFN-β, while both phytocannabinoids failed to impact TLR4-induced IκB-α degradation and TNF-α/CXCL8 expression. The role of CB<sub>1</sub>, CB<sub>2</sub> and PPARγ receptors in mediating the effect of THC and CBD on MyD88-independent signalling was investigated. TLRs are attractive therapeutic targets given their role in inflammation and initiation of adaptive immunity, and data herein indicate that both CBD and THC preferentially modulate TLR3 and TLR4 signalling via MyD88-independent mechanisms in macrophages. This offers mechanistic insight into the role of phytocannabinoids in modulating cellular inflammation.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fitzpatrick</LastName><ForeName>John-Mark</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Minogue</LastName><ForeName>Eleanor</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Curham</LastName><ForeName>Lucy</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tyrrell</LastName><ForeName>Harry</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gavigan</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hind</LastName><ForeName>William</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>GW Research Ltd, Sovereign House, Vision Park, Histon, CB24 9BZ, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Downer</LastName><ForeName>Eric J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland. Electronic address: edowner@tcd.ie.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>03</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Neuroimmunol</MedlineTA><NlmUniqueID>8109498</NlmUniqueID><ISSNLinking>0165-5728</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C507779">MYD88 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053594">Myeloid Differentiation Factor 88</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C495344">TLR3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C495345">TLR4 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051196">Toll-Like Receptor 3</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051197">Toll-Like Receptor 4</NameOfSubstance></Chemical><Chemical><RegistryNumber>19GBJ60SN5</RegistryNumber><NameOfSubstance UI="D002185">Cannabidiol</NameOfSubstance></Chemical><Chemical><RegistryNumber>7J8897W37S</RegistryNumber><NameOfSubstance UI="D013759">Dronabinol</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002185" MajorTopicYN="N">Cannabidiol</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013759" MajorTopicYN="N">Dronabinol</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053594" MajorTopicYN="N">Myeloid Differentiation Factor 88</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051196" MajorTopicYN="N">Toll-Like Receptor 3</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051197" MajorTopicYN="N">Toll-Like Receptor 4</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Cannabidiol</Keyword><Keyword MajorTopicYN="Y">IRF</Keyword><Keyword MajorTopicYN="Y">Inflammation</Keyword><Keyword MajorTopicYN="Y">Innate immunity</Keyword><Keyword MajorTopicYN="Y">Macrophages</Keyword><Keyword MajorTopicYN="Y">NF-κB</Keyword><Keyword MajorTopicYN="Y">TLR</Keyword><Keyword MajorTopicYN="Y">Tetrahydrocannabinol</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Supplementary data to this article can be found online at https://doi.org/10.1016/j.jneuroim.2020.577217.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>01</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>03</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>03</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32244040</ArticleId><ArticleId IdType="pii">S0165-5728(20)30057-6</ArticleId><ArticleId IdType="doi">10.1016/j.jneuroim.2020.577217</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Irlande (pays)</li><li>Royaume-Uni</li></country></list><tree><country name="Irlande (pays)"><noRegion><name sortKey="Fitzpatrick, John Mark" sort="Fitzpatrick, John Mark" uniqKey="Fitzpatrick J" first="John-Mark" last="Fitzpatrick">John-Mark Fitzpatrick</name></noRegion><name sortKey="Curham, Lucy" sort="Curham, Lucy" uniqKey="Curham L" first="Lucy" last="Curham">Lucy Curham</name><name sortKey="Downer, Eric J" sort="Downer, Eric J" uniqKey="Downer E" first="Eric J" last="Downer">Eric J. Downer</name><name sortKey="Gavigan, Philip" sort="Gavigan, Philip" uniqKey="Gavigan P" first="Philip" last="Gavigan">Philip Gavigan</name><name sortKey="Minogue, Eleanor" sort="Minogue, Eleanor" uniqKey="Minogue E" first="Eleanor" last="Minogue">Eleanor Minogue</name><name sortKey="Tyrrell, Harry" sort="Tyrrell, Harry" uniqKey="Tyrrell H" first="Harry" last="Tyrrell">Harry Tyrrell</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Hind, William" sort="Hind, William" uniqKey="Hind W" first="William" last="Hind">William Hind</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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