1,25-Dihydroxyvitamin D3 Suppresses TLR8 Expression and TLR8-Mediated Inflammatory Responses in Monocytes In Vitro and Experimental Autoimmune Encephalomyelitis In Vivo
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"1,25-Dihydroxyvitamin D3 Suppresses TLR8 Expression and TLR8-Mediated Inflammatory Responses in Monocytes In Vitro and Experimental Autoimmune Encephalomyelitis In Vivo", "type"=>"journal", "authors"=>[{"first_name"=>"Bo", "last_name"=>"Li", "scopus_author_id"=>"57190187997"}, {"first_name"=>"David J.", "last_name"=>"Baylink", "scopus_author_id"=>"35473628500"}, {"first_name"=>"Chandra", "last_name"=>"Deb", "scopus_author_id"=>"24437125300"}, {"first_name"=>"Claudia", "last_name"=>"Zannetti", "scopus_author_id"=>"8048312500"}, {"first_name"=>"Fatima", "last_name"=>"Rajaallah", "scopus_author_id"=>"55623418800"}, {"first_name"=>"Weirong", "last_name"=>"Xing", "scopus_author_id"=>"35301325100"}, {"first_name"=>"Michael H.", "last_name"=>"Walter", "scopus_author_id"=>"12774463700"}, {"first_name"=>"K. H.William", "last_name"=>"Lau", "scopus_author_id"=>"7401560017"}, {"first_name"=>"Xuezhong", "last_name"=>"Qin", "scopus_author_id"=>"7202154947"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84875035826", "pmid"=>"23516559", "sgr"=>"84875035826", "doi"=>"10.1371/journal.pone.0058808", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"368535215"}, "id"=>"700e56d6-2d15-3479-baeb-b8c06ad247cf", "abstract"=>"1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) suppresses autoimmunity and inflammation; however, the mechanism of its action has not been fully understood. We sought in this study to determine whether the anti-immune/anti-inflammatory action of 1,25(OH)2D3 is in part mediated through an interplay between 1,25(OH)2D3 and toll-like receptor (TLR)7/8 signaling. 1,25(OH)2D3 treatment prior to and/or following experimental autoimmune encephalomyelitis (EAE) induction effectively reduced inflammatory cytokine expression in the spinal cord and ameliorated EAE. These effects were accompanied with a reduction in expression of several TLRs with the most profound effect observed for TLR8. The expression of TLR8 adaptor protein MyD88 was also significantly reduced by 1,25(OH)2D3. To determine the molecular mechanism by which 1,25(OH)2D3 suppresses EAE induction of TLR8 and inflammatory cytokine expression, we evaluated whether 1,25(OH)2D3 can directly inhibit TLR8 signaling and the resulting inflammatory responses in human THP-1 monocytes. 1,25(OH)2D3 treatment not only significantly reduced TLR8 expression but also the expression or activity of MyD88, IRF-4, IRF-7 and NF-kB in monocytes challenged with TLR8 ligands. TLR8 promoter-luciferase reporter assays indicated that 1,25(OH)2D3 decreases TLR8 mRNA level in part via inhibiting TLR8 gene transcription activity. As a result of inhibition on TLR8 signaling cascade at various stages, 1,25(OH)2D3 significantly diminished the TLR8 target gene expression (TNF-α and IL-1β). In summary, our novel findings suggest that TLR8 is a new target of 1,25(OH)2D3 and may mediate the anti-inflammatory action of 1,25(OH)2D3. Our findings also point to a destructive role of TLR8 in EAE and shed lights on pathogenesis of multiple sclerosis.", "link"=>"http://www.mendeley.com/research/125dihydroxyvitamin-d3-suppresses-tlr8-expression-tlr8mediated-inflammatory-responses-monocytes-vitr", "reader_count"=>27, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>7, "Neuroscience"=>1, "Psychology"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84875035826"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84875035826?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84875035826&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84875035826&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84875035826", "dc:identifier"=>"SCOPUS_ID:84875035826", "eid"=>"2-s2.0-84875035826", "dc:title"=>"1,25-Dihydroxyvitamin D3 Suppresses TLR8 Expression and TLR8-Mediated Inflammatory Responses in Monocytes In Vitro and Experimental Autoimmune Encephalomyelitis In Vivo", "dc:creator"=>"Li B.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"8", "prism:issueIdentifier"=>"3", "prism:pageRange"=>nil, "prism:coverDate"=>"2013-03-14", "prism:coverDisplayDate"=>"14 March 2013", "prism:doi"=>"10.1371/journal.pone.0058808", "citedby-count"=>"27", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Loma Linda University School of Medicine", "affiliation-city"=>"Loma Linda", "affiliation-country"=>"United States"}], "pubmed-id"=>"23516559", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e58808", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0058808", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"40", "xml_views"=>"2", "html_views"=>"256"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"26", "xml_views"=>"1", "html_views"=>"80"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"20", "xml_views"=>"4", "html_views"=>"93"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"47"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"16", "xml_views"=>"2", "html_views"=>"54"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"19", "xml_views"=>"2", "html_views"=>"36"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"69"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"2", "html_views"=>"51"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"43"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"14"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"65"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"83"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"2", "html_views"=>"28"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"26"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"14"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"3"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"3", "html_views"=>"5"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"2"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"2"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"1"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"3"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"0"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"4"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"0"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"1"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/988306"], "description"=>"<p>EAE was induced by immunonization with MOG (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#s2\" target=\"_blank\"><i>Material & Methods</i></a>). Mice were injected i.p. with 2 µg of 1,25(OH)<sub>2</sub>D<sub>3</sub> one day before MOG injection and then 0.1 µg 1,25(OH)<sub>2</sub>D<sub>3</sub> every other day till day 14 post-MOG injection. Body weight (<b>A</b>) and clinical score (<b>B</b>) were determined at day 14 post-MOG injection. Data represent the means ± SEM (n = 7) from two independent experiments. *** <i>P</i><0.001.</p>", "links"=>[], "tags"=>["protected", "mice"], "article_id"=>652827, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_1_25_OH_2_D_3_treatment_significantly_protected_mice_from_development_of_EAE_/652827", "title"=>"1,25(OH)<sub>2</sub>D<sub>3</sub> treatment significantly protected mice from development of EAE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/988309"], "description"=>"<p>Animal treatments were described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#pone-0058808-g001\" target=\"_blank\">Figure 1</a> legend. Fourteen days after MOG injection, spinal cords were collected for RNA isolation and immunohistochemical analysis. (<b>A</b>) Representative F4/80 immunostaining of frozen spinal cord sections. Spinal cords from MOG treated mice showed dense mononuclear cell infiltration (circle). The number of F4/80-positive cells were reduced following treatment of EAE mice with 1,25(OH)<sub>2</sub>D<sub>3</sub>. Three mice were analyzed in each group. Original magnification was X10. (<b>B–D</b>) Real-time RT-PCR analysis of the inflammatory gene expression (TNF-α, INF-γ and IL-17) in spinal cord. (<b>E</b>) Serum concentration of IL-17 was determined by ELISA. Data represent the means ± SEM (n = 4) from one of two independent experiments. * <i>P</i><0.05; ** <i>P</i><0.01; *** <i>P</i><0.001.</p>", "links"=>[], "tags"=>["inflammatory", "infiltration", "cytokine", "mog-induced"], "article_id"=>652828, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Suppressive_effect_of_1_25_OH_2_D_3_on_inflammatory_cell_infiltration_and_inflammatory_cytokine_production_in_MOG_induced_EAE_/652828", "title"=>"Suppressive effect of 1,25(OH)<sub>2</sub>D<sub>3</sub> on inflammatory cell infiltration and inflammatory cytokine production in MOG-induced EAE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:45:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/988312"], "description"=>"<p>(<b>A</b>) Real-time RT-PCR analysis of expression of the key TLRs in the spinal cord (Prevention model, refer to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#pone-0058808-g001\" target=\"_blank\">Figure 1</a> legend for 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment scheme). The mRNA levels of TLR3 and TLR8 were significantly increased in EAE spinal cords. 1,25(OH)<sub>2</sub>D<sub>3</sub> only significantly reduced TLR8 mRNA level. Data shown are the means ± SEM (n = 4) from one of two independent experiments. (<b>B</b>) Real-time RT-PCR analysis of expression of the key TLRs in the spinal cord (Treatment model). Mice were injected with 1,25(OH)<sub>2</sub>D<sub>3</sub> beginning at day 7 post-MOG injection (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#s2\" target=\"_blank\"><i>Material and Methods</i></a>). Expression of all 4 TLRs analyzed were significantly induced by EAE and reduced by 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment. Data shown are the means ± SEM (n = 4) from one of two independent experiments. In both treatment and prevention models, TLR8 mRNA level showed the highest magnitude of induction by EAE and was significantly down-regulated by 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment. * <i>P</i><0.05; ** <i>P</i><0.01. (<b>C</b>) Representative TLR8 immunostaining of spinal cord sections. Animal treatments were described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#pone-0058808-g001\" target=\"_blank\">Figure 1</a> legend. Three mice were analyzed in each group. The magnification was X10 (upper panels). (<b>D</b>) FACS analysis of intracellular TLR7 and 8 expressions in the spinal cord in both models. Mononuclear cells were isolated using pooled spinal cords from 2–3 mice each group by Percoll gradients (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#s2\" target=\"_blank\"><i>Material and Methods</i></a>). Data are representative of two independent analyses.</p>", "links"=>[], "tags"=>["reduced", "eae-induced", "tlr8", "spinal"], "article_id"=>652831, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Treatment_with_1_25_OH_2_D_3_reduced_EAE_induced_expression_of_TLR8_in_the_spinal_cord_/652831", "title"=>"Treatment with 1,25(OH)<sub>2</sub>D<sub>3</sub> reduced EAE-induced expression of TLR8 in the spinal cord.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:46:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/988313"], "description"=>"<p>Animal treatments and spinal cord sample collections were described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#pone-0058808-g001\" target=\"_blank\">Figure 1</a> legend. (<b>A–D</b>) Real-time RT-PCR analysis of the relative levels of mRNA for MyD88 (<b>A</b>), IRF-4 (<b>B</b>), IBP (<b>C</b>), and Schalfen-4 (<b>D</b>). These downstream mediators of TLR8 signaling showed significant increase of mRNA expression in EAE and this increase was completely prevented by 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment. Data represent the means± SEM (n = 4) from one of two independent experiments. * <i>P</i><0.05; ** <i>P</i><0.01.</p>", "links"=>[], "tags"=>["inhibits", "activation", "tlr8", "cascade"], "article_id"=>652832, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_1_25_OH_2_D_3_inhibits_activation_of_TLR8_signaling_cascade_in_EAE_/652832", "title"=>"1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits activation of TLR8 signaling cascade in EAE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:46:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/988315"], "description"=>"<p>(<b>A–B</b>) Human monocyte THP-1 cells were pretreated with 1,25(OH)<sub>2</sub>D<sub>3</sub> (100 nM) for 30 min and then stimulated with CL075 (1 µg/ml) or ssRNA (5 µg/ml) for 20 h. (<b>C–D</b>) THP-1 cells were pretreated with different doses of 1,25(OH)<sub>2</sub>D<sub>3</sub> (0.1–200 nM) for 30 min and then incubated with CL075 (1 µg/ml) for additional 20 h. TNF-α and IL-1β mRNA levels were measured by real-time RT-PCR. Data shown are means ± SEM (n = 4) and are representative of three independent experiments. *** <i>P</i><0.001.</p>", "links"=>[], "tags"=>["inhibits", "tlr8-mediated", "inflammatory", "cytokine", "thp-1"], "article_id"=>652834, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_1_25_OH_2_D_3_inhibits_TLR8_mediated_inflammatory_cytokine_expression_in_human_THP_1_monocytes_/652834", "title"=>"1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits TLR8-mediated inflammatory cytokine expression in human THP-1 monocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:46:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/988316"], "description"=>"<p>THP-1 cell treatment was described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#pone-0058808-g005\" target=\"_blank\">Figure 5A-B</a> legend. (<b>A</b>) mRNA level of TLR8 was subsequently determined by real-time RT-PCR. Data shown here represent means ± SEM (n = 4) and are representative of three independent experiments. (<b>B</b>) Intracellular expression of TLR8 was analyzed by FACS analysis using PE-conjugated anti-TLR8 antibody (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#s2\" target=\"_blank\"><i>Material & Methods</i></a>). Isotype control antibody was used as negative control for non-specific TLR8 staining. A representative histogram plot was shown here from three independent experiments. (<b>C</b>) The THP-1 cells were co-transfected with TLR8 promoter-luciferase and TK-Renilla plasmid as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#s2\" target=\"_blank\"><i>Material and Methods</i></a>. After 24 h, cells were pretreated with 1,25(OH)<sub>2</sub>D<sub>3</sub> (100 nM) for 30 min and then stimulated with CL075 (4 µg/ml) for 20 h. The TLR8 promoter activity was presented as the ratio of luciferase activity to TK-Renilla activity. The data shown are means ± SEM (n = 4) and representative of two independent experiments. * <i>P</i><0.05; ** <i>P</i><0.01; ***, <i>P</i><0.001.</p>", "links"=>[], "tags"=>["inhibits", "tlr8", "agonist-induced"], "article_id"=>652835, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_1_25_OH_2_D_3_inhibits_TLR8_agonist_induced_TLR8_expression_in_human_monocytes_/652835", "title"=>"1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits TLR8 agonist-induced TLR8 expression in human monocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:46:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/988317"], "description"=>"<p>(<b>A–C</b>) THP-1 cell treatment was described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#pone-0058808-g005\" target=\"_blank\">Figure 5A–B</a> legend. Cells were collected and subjected to RNA and protein extraction. mRNA levels of MyD88 (<b>A</b>), IRF-4 (<b>B</b>) and IRF-7 (<b>C</b>) were determined by real-time RT-PCR. Data represent means ± SEM (n = 4) and are representative of three independent experiments. (<b>D</b>) Western blotting for NF-kB and IkB-I protein detection was performed on total cell lysates from THP-1cells stimulated with CL075 (1 µg/ml) in the presence of vehicle or 1,25(OH)<sub>2</sub>D<sub>3</sub> (100 nM) for 20 h. Representative results were obtained from two independent experiments. (<b>E</b>) The THP-1 cells were co-transfected with NF-kB promoter luciferase and TK-Renilla plasmid (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058808#s2\" target=\"_blank\"><i>Materials and Methods</i></a>). After 24 h, the cells were pretreated with 1,25(OH)<sub>2</sub>D<sub>3</sub> (100 nM) for 30 min and then stimulated with CL075 (4 µg/ml) for 20 h. Luciferase activity was measured and presented as the ratio of luciferase activity to TK-Renilla activity. The data shown are means ± SEM (n = 4) and are representative of three independent experiments. * <i>P</i><0.05; ** <i>P</i><0.01; *** <i>P</i><0.001.</p>", "links"=>[], "tags"=>["inhibits", "tlr8", "agonist-induced", "mediators"], "article_id"=>652836, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_1_25_OH_2_D_3_inhibits_TLR8_agonist_induced_expression_of_key_mediators_of_TLR8_signaling_in_human_monocytes_/652836", "title"=>"1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits TLR8 agonist-induced expression of key mediators of TLR8 signaling in human monocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-15 13:47:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/988318", "https://ndownloader.figshare.com/files/988319", "https://ndownloader.figshare.com/files/988321", "https://ndownloader.figshare.com/files/988322"], "description"=>"<div><p>1,25-Dihydroxyvitamin D3 (1,25(OH)<sub>2</sub>D<sub>3</sub>) suppresses autoimmunity and inflammation; however, the mechanism of its action has not been fully understood. We sought in this study to determine whether the anti-immune/anti-inflammatory action of 1,25(OH)<sub>2</sub>D<sub>3</sub> is in part mediated through an interplay between 1,25(OH)<sub>2</sub>D<sub>3</sub> and toll-like receptor (TLR)7/8 signaling. 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment prior to and/or following experimental autoimmune encephalomyelitis (EAE) induction effectively reduced inflammatory cytokine expression in the spinal cord and ameliorated EAE. These effects were accompanied with a reduction in expression of several TLRs with the most profound effect observed for TLR8. The expression of TLR8 adaptor protein MyD88 was also significantly reduced by 1,25(OH)<sub>2</sub>D<sub>3</sub>. To determine the molecular mechanism by which 1,25(OH)<sub>2</sub>D<sub>3</sub> suppresses EAE induction of TLR8 and inflammatory cytokine expression, we evaluated whether 1,25(OH)<sub>2</sub>D<sub>3</sub> can directly inhibit TLR8 signaling and the resulting inflammatory responses in human THP-1 monocytes. 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment not only significantly reduced TLR8 expression but also the expression or activity of MyD88, IRF-4, IRF-7 and NF-kB in monocytes challenged with TLR8 ligands. TLR8 promoter-luciferase reporter assays indicated that 1,25(OH)<sub>2</sub>D<sub>3</sub> decreases TLR8 mRNA level in part via inhibiting TLR8 gene transcription activity. As a result of inhibition on TLR8 signaling cascade at various stages, 1,25(OH)<sub>2</sub>D<sub>3</sub> significantly diminished the TLR8 target gene expression (TNF-α and IL-1β). In summary, our novel findings suggest that TLR8 is a new target of 1,25(OH)<sub>2</sub>D<sub>3</sub> and may mediate the anti-inflammatory action of 1,25(OH)<sub>2</sub>D<sub>3</sub>. Our findings also point to a destructive role of TLR8 in EAE and shed lights on pathogenesis of multiple sclerosis.</p> </div>", "links"=>[], "tags"=>["d3", "suppresses", "tlr8", "tlr8-mediated", "inflammatory", "responses", "monocytes", "vitro", "autoimmune", "encephalomyelitis", "vivo"], "article_id"=>652837, "categories"=>["Immunology"], "users"=>["Bo Li", "David J. Baylink", "Chandra Deb", "Claudia Zannetti", "Fatima Rajaallah", "Weirong Xing", "Michael H. Walter", "K.-H. William Lau", "Xuezhong Qin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058808.s001", "https://dx.doi.org/10.1371/journal.pone.0058808.s002", "https://dx.doi.org/10.1371/journal.pone.0058808.s003", "https://dx.doi.org/10.1371/journal.pone.0058808.s004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/1_25_Dihydroxyvitamin_D3_Suppresses_TLR8_Expression_and_TLR8_Mediated_Inflammatory_Responses_in_Monocytes_In_Vitro_and_Experimental_Autoimmune_Encephalomyelitis_In_Vivo__/652837", "title"=>"1,25-Dihydroxyvitamin D3 Suppresses TLR8 Expression and TLR8-Mediated Inflammatory Responses in Monocytes In Vitro and Experimental Autoimmune Encephalomyelitis In Vivo", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-15 13:47:44"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"26", "full-text"=>"27", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"60", "full-text"=>"58", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"26", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"32", "full-text"=>"42", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"22", "full-text"=>"20", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"3", "abstract"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"25", "full-text"=>"24", "pdf"=>"39", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"30", "full-text"=>"32", "pdf"=>"31", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"22", "full-text"=>"30", "pdf"=>"22", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"32", "full-text"=>"34", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"27", "full-text"=>"27", "pdf"=>"10", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"3", "cited-by"=>"2", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"21", "full-text"=>"22", "pdf"=>"13", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"26", "full-text"=>"24", "pdf"=>"19", "abstract"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"23", "full-text"=>"27", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"1", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"19", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"19", "full-text"=>"26", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"21", "full-text"=>"23", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"23", "full-text"=>"23", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"21", "pdf"=>"8", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"13", "pdf"=>"3", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"17", "full-text"=>"11", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"15", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"1", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"9", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"19", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"3", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[275, 472, 605, 720, 822, 921, 1013, 1106, 1200, 1289, 1378, 1459, 1531]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[272, 466, 589, 702, 806, 903, 995, 1086, 1176, 1258, 1347, 1422, 1493]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[256, 449, 572, 676, 775, 866, 955, 1041, 1127, 1213, 1290, 1370, 1437]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Anatomy and physiology", "average_usage"=>[253, 430]}, {"subject_area"=>"/Medicine and health sciences/Clinical medicine", "average_usage"=>[263, 451, 582, 699, 797, 889, 969, 1045, 1134, 1215, 1284, 1362, 1412]}, {"subject_area"=>"/Medicine and health sciences/Neurology", "average_usage"=>[271, 485, 617, 733, 835, 933, 1026, 1115, 1207, 1294, 1386, 1475, 1543]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[267, 466, 592, 709, 806, 901, 989, 1075, 1162, 1254, 1342, 1424, 1486]}]}
Loading … Spinner
There are currently no alerts