Human β-D-3 Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid
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{"title"=>"Human β-D-3 Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid", "type"=>"journal", "authors"=>[{"first_name"=>"Fiona", "last_name"=>"Semple", "scopus_author_id"=>"35800209900"}, {"first_name"=>"Heather", "last_name"=>"MacPherson", "scopus_author_id"=>"7006062934"}, {"first_name"=>"Sheila", "last_name"=>"Webb", "scopus_author_id"=>"56871283900"}, {"first_name"=>"Fiona", "last_name"=>"Kilanowski", "scopus_author_id"=>"6602361009"}, {"first_name"=>"Laura", "last_name"=>"Lettice", "scopus_author_id"=>"6602126520"}, {"first_name"=>"Sarah L.", "last_name"=>"McGlasson", "scopus_author_id"=>"56801100700"}, {"first_name"=>"Ann P.", "last_name"=>"Wheeler", "scopus_author_id"=>"37009442600"}, {"first_name"=>"Valerie", "last_name"=>"Chen", "scopus_author_id"=>"56967640000"}, {"first_name"=>"Glenn L.", "last_name"=>"Millhauser", "scopus_author_id"=>"7005734884"}, {"first_name"=>"Lauren", "last_name"=>"Melrose", "scopus_author_id"=>"25951441300"}, {"first_name"=>"Donald J.", "last_name"=>"Davidson", "scopus_author_id"=>"7402300034"}, {"first_name"=>"Julia R.", "last_name"=>"Dorin", "scopus_author_id"=>"7007101594"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"607579349", "sgr"=>"84953298987", "issn"=>"15537404", "pmid"=>"26646717", "scopus"=>"2-s2.0-84953298987", "doi"=>"10.1371/journal.pgen.1005673"}, "id"=>"e5beaa63-a82c-3ef0-b5d5-0ece444f14fd", "abstract"=>"Human β-defensin 3 (hBD3) is a cationic host defence peptide and is part of the innate immune response. HBD3 is present on a highly copy number variable block of six β-defensin genes, and increased copy number is associated with the autoimmune disease psoriasis. It is not known how this increase influences disease development, but psoriasis is a T cell-mediated disease and activation of the innate immune system is required for the initial trigger that leads to the amplification stage. We investigated the effect of hBD3 on the response of primary macrophages to various TLR agonists. HBD3 exacerbated the production of type I Interferon-β in response to the viral ligand mimic polyinosinic:polycytidylic acid (polyI:C) in both human and mouse primary cells, although production of the chemokine CXCL10 was suppressed. Compared to polyI:C alone, mice injected with both hBD3 peptide and polyI:C also showed an enhanced increase in Interferon-β. Mice expressing a transgene encoding hBD3 had elevated basal levels of Interferon-β, and challenge with polyI:C further increased this response. HBD3 peptide increased uptake of polyI:C by macrophages, however the cellular response and localisation of polyI:C in cells treated contemporaneously with hBD3 or cationic liposome differed. Immunohistochemistry showed that hBD3 and polyI:C do not co-localise, but in the presence of hBD3 less polyI:C localises to the early endosome. Using bone marrow derived macrophages from knockout mice we demonstrate that hBD3 suppresses the polyI:C-induced TLR3 response mediated by TICAM1 (TRIF), while exacerbating the cytoplasmic response through MDA5 (IFIH1) and MAVS (IPS1/CARDIF). Thus, hBD3, a highly copy number variable gene in human, influences cellular responses to the viral mimic polyI:C implying that copy number may have a significant phenotypic effect on the response to viral infection and development of autoimmunity in humans.", "link"=>"http://www.mendeley.com/research/human-%CE%B2d3-exacerbates-mda5-suppresses-tlr3-responses-viral-molecular-pattern-mimic-polyinosinicpolyc", "reader_count"=>7, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>4, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4295005"], "description"=>"<p>(A) Wild type (wt) mice were injected intraperitoneally (i.p.) with polyI:C (pI:C) (100μg/mouse) in the presence or absence of hBD3 (20μg/mouse) as indicated and cytokines measured by ELISA. (B) hBD3-Tg and DSRed-Tg control mice were injected i.p. with pI:C (100μg/mouse), after 4hr serum cytokine levels were measured by ELISA. (C) Wt and hBD3-Tg mice were bled and serum IFN-β measured by ELISA**p<0.01, *p<0.05 student t-test (n = 6 separate mice for each treatment group).</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621472, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HBD3_enhances_the_effects_of_polyI_C_in_vivo_/1621472", "title"=>"HBD3 enhances the effects of polyI:C <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4295014"], "description"=>"<p>BMDM from 3 separate wildtype mice were treated with pI:C, or pI:C pre-complexed with lipofectamine (at 1:100 dilution, 10μl/ml for 15min), in the presence or absence of hBD3. After 18hr cells were, (A) analysed by flow cytometry and culture supernatants were analysed by ELISA to measure (B) CXCL10 and (C) IFNβ ***p<0.001, **p<0.01, *p<0.05. (D) BMDM, grown on glass slides, were treated with 10mg/ml FITC-pI:C, without and with hBD3, without and with lipofectamine as labelled. Representative slides of each treatment visualised by confocal microscopy, are shown.</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621473, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBD3_does_not_mimic_the_effects_of_lipofectamine_/1621473", "title"=>"hBD3 does not mimic the effects of lipofectamine.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4295020"], "description"=>"<p>Wildtype BMDM were treated with (A)TAMRA-hBD3 or (B) FITC-polyI:C (pI:C) and imaged at 2 (i),10 (ii) and 30 (iii) minutes. BMDM treated for 30 min with (C) FITC-pI:C (green) or (D) TAMRA-hBD3 were stained with anti-EEA1 antibody. DAPI (4',6-Diamidino-2-Phenylindole, Dihydrochloride) staining shown in C(i) and D(i); FITC-pI:C (green) and TAMRA-hBD3 (red) are shown in C(ii) and D(ii) respectively; EEA1 staining is shown in C(iii) and D(iii) (pseudocoloured red and green respectively); pI:C and hBD3 colocalisation with EEA1 are demonstrated C(iv) in and D(iv) merged images respectively, with Pearson co-efficients of r = 0.615(C(iv)) and r = 0.205(D(iv)). (E-i-viii) BMDM were treated (30 min) with FITC-pI:C and TAMRA-hBD3 and immunostained with EEA1-1 antibody. One representative cell from each slide is shown with filters allowing visualisation of single entities, E(i) DAPI staining for nucleus; E(ii) TAMRA-hBD3; E(iii) FITC-pI:C; E(iv) EEA1-1-Cy5 (blue), E(v) merge of Eii,iii and iv. E(vi)-(viii) are merged images showing only two components to assess co-localisation, (vi) polyI:C (green), EEA1-1 (pseudocoloured red) and hBD3 invisible; (vii) polyI:C (green) hBD3 (red) and EEA1-1 invisible; (viii) hBD3 (red) and EEA1-1(pseudocoloured green) and polyI:C invisible. Images are representative of all cells treated, and visualised by confocal microscopy. Additional single colour images of EEA1 pseudocolouring to complement 5E are shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005673#pgen.1005673.s003\" target=\"_blank\">S3 Fig</a>. Scale bars indicate 10 microns.</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621474, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBD3_enters_cells_more_quickly_than_polyI_C_and_does_not_co_localise_with_polyI_C_or_endosome_marker_EEA1_/1621474", "title"=>"hBD3 enters cells more quickly than polyI:C and does not co-localise with polyI:C or endosome marker EEA1.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4295026"], "description"=>"<p>BMDM from wildtype, <i>Mavs(</i>-/-) or <i>Ticam1</i>(-/-) mice were treated with 10μg/ml pI:C in the presence or absence of hBD3. After 18hr cell culture supernatants were analysed by ELISA to measure (A) Interferon-β (IFNβ) and (B) CXCL10 **p<0.01, *p<0.05 (In each group BMDM were from 4 separate mice).</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621475, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g006"], "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBD3_inhibits_TICAM1_signalling_but_enhances_MAVS_dependent_signalling_/1621475", "title"=>"hBD3 inhibits TICAM1 signalling but enhances MAVS-dependent signalling.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4295029"], "description"=>"<p>(A) BMDM from wildtype and <i>Mavs</i>(-/-) mice were treated with 500ng/ml 5’ppp in the presence and absence of 5μg/ml hBD3 (B) wildtype and <i>Mda5</i> (-/-) BMDM were treated with pI:C in the presence and absence of hBD3. **p<0.01, *p<0.05, Student t-test. (In each group BMDM were from 4 separate mice).</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621476, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBD3_inhibits_RIGI_signalling_and_enhances_MDA5_signalling_/1621476", "title"=>"hBD3 inhibits RIGI signalling and enhances MDA5 signalling.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4295038"], "description"=>"<p>Pale arrows indicate relative amounts of HMW polyI:C accessing different areas of the cell under our three different treatment conditions. The cell membrane is indicated by a double line, MAVS is located adjacent to the mitochondria. MDA5 is free in cytoplasm but goes to MAVS adaptor to generate the signalling cascade that results in IRF activation and production of Interferon-β (IFNβ). The black arrows indicate the strength of signalling that results in IFNβ or CXCL10 production with the dotted line indicating least signalling and the widest line indicating most signalling. Compared to polyI:C alone, hBD3 increases IFNβ production from MDA5 signalling and despite reducing the amount from TLR3, overall IFNβ levels rise. CXCL10 production from TLR3 is reduced by polyI:C in the presence of hBD3 because less is located at the endosome available for TLR3 signalling. In the presence of Lipofectamine, polyI:C production by TLR3/TICAM1 of CXCL10 increases due to increased endosomal signalling.</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621477, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_hBD3_and_Lipofectamine_2000_interaction_with_HMW_polyI_C_/1621477", "title"=>"Schematic of hBD3 and Lipofectamine 2000 interaction with HMW polyI:C.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4294957", "https://ndownloader.figshare.com/files/4294963", "https://ndownloader.figshare.com/files/4294966", "https://ndownloader.figshare.com/files/4294972", "https://ndownloader.figshare.com/files/4294975", "https://ndownloader.figshare.com/files/4294981"], "description"=>"<div><p>Human β-defensin 3 (hBD3) is a cationic host defence peptide and is part of the innate immune response. HBD3 is present on a highly copy number variable block of six β-defensin genes, and increased copy number is associated with the autoimmune disease psoriasis. It is not known how this increase influences disease development, but psoriasis is a T cell-mediated disease and activation of the innate immune system is required for the initial trigger that leads to the amplification stage. We investigated the effect of hBD3 on the response of primary macrophages to various TLR agonists. HBD3 exacerbated the production of type I Interferon-β in response to the viral ligand mimic polyinosinic:polycytidylic acid (polyI:C) in both human and mouse primary cells, although production of the chemokine CXCL10 was suppressed. Compared to polyI:C alone, mice injected with both hBD3 peptide and polyI:C also showed an enhanced increase in Interferon-β. Mice expressing a transgene encoding hBD3 had elevated basal levels of Interferon-β, and challenge with polyI:C further increased this response. HBD3 peptide increased uptake of polyI:C by macrophages, however the cellular response and localisation of polyI:C in cells treated contemporaneously with hBD3 or cationic liposome differed. Immunohistochemistry showed that hBD3 and polyI:C do not co-localise, but in the presence of hBD3 less polyI:C localises to the early endosome. Using bone marrow derived macrophages from knockout mice we demonstrate that hBD3 suppresses the polyI:C-induced TLR3 response mediated by TICAM1 (TRIF), while exacerbating the cytoplasmic response through MDA5 (IFIH1) and MAVS (IPS1/CARDIF). Thus, hBD3, a highly copy number variable gene in human, influences cellular responses to the viral mimic polyI:C implying that copy number may have a significant phenotypic effect on the response to viral infection and development of autoimmunity in humans.</p></div>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621478, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.s001", "https://dx.doi.org/10.1371/journal.pgen.1005673.s002", "https://dx.doi.org/10.1371/journal.pgen.1005673.s003", "https://dx.doi.org/10.1371/journal.pgen.1005673.s004", "https://dx.doi.org/10.1371/journal.pgen.1005673.s005", "https://dx.doi.org/10.1371/journal.pgen.1005673.s006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Human_946_D_3_Exacerbates_MDA5_but_Suppresses_TLR3_Responses_to_the_Viral_Molecular_Pattern_Mimic_Polyinosinic_Polycytidylic_Acid_/1621478", "title"=>"Human β-D-3 Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4294987"], "description"=>"<p>(A) BMDM from 3 separate wildtype (wt) mice were incubated overnight with HKLM (Heat Killed <i>Listeria monocytogenes</i>) (TLR2 ligand), FSL-1 (synthetic lipoprotein Pam2CGDPKHPKSF derived from <i>Mycoplasma salivarium) (TLR2/6 ligand)</i>, LTA (Lipoteichoic acid from <i>S. aureus</i> (TLR2 ligand), Pam3CSK4 (synthetic mimic of bacterial triacylated lipopeptide (TLR2/1 ligand), R848 (imidazoquinoline compound (TLR7 ligand), CpG (TLR9), TLR4 (LPS) or (B) HMW polyI:C (pI:C) (TLR3/RLR agonist) (10µg/ml) with and without hBD3. (C) PMA-differentiated THP-1 cells were treated with HMW polyI:C (10µg/ml) with or without 5 mg/ml hBD3. TNF-α, IL-6, IL-8 and CXCL10 induction were measured by ELISA *p≤0.05, **p≤0.01 student t-test (D) Human primary PBMDM were exposed to polyI:C as indicated, Interferon-β (IFNβ) gene expression was measured by qRT-PCR. ***p<0.001, 2-way ANOVA.</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621468, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_hBD3_exacerbates_stimulation_by_the_viral_mimic_HMW_polyI_C_but_does_not_increase_stimulation_by_other_TLR_ligands_/1621468", "title"=>"hBD3 exacerbates stimulation by the viral mimic HMW polyI:C but does not increase stimulation by other TLR ligands", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/4294996"], "description"=>"<p>(A) BMDM from 3 separate mice were treated for 18hr with pI:C (10μg/ml) in the presence and absence of reducing concentration of hBD3 or (B) modified hBD3-cys:ser as indicated and IFNβ, CXCL10 and TNFα measured by ELISA. Image in B shows BMDM treated with 0.5μg/ml TAMRA-hBD3-cys:ser (10 min) observed by fluorescent microscopy. Scale bar 10μM.</p>", "links"=>[], "tags"=>["increase influences disease development", "cationic host defence peptide", "TICAM", "Suppresses TLR 3 Responses", "IPS", "MAVS", "IFIH", "chemokine CXCL 10", "hBD 3", "hBD 3 peptide", "copy number", "HBD 3 peptide", "MDA", "TRIF", "HBD 3", "polyI", "response", "transgene encoding hBD 3"], "article_id"=>1621471, "categories"=>["Biochemistry", "Microbiology", "Genetics", "Molecular Biology", "Biotechnology", "Chemical Sciences not elsewhere classified", "Ecology", "Immunology", "Developmental Biology", "Cancer", "Mental Health", "Infectious Diseases", "Virology"], "users"=>["Fiona Semple", "Heather MacPherson", "Sheila Webb", "Fiona Kilanowski", "Laura Lettice", "Sarah L. McGlasson", "Ann P. Wheeler", "Valerie Chen", "Glenn L. Millhauser", "Lauren Melrose", "Donald J. Davidson", "Julia R. Dorin"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005673.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HBD3_effect_on_Interferon_946_response_to_polyI_C_is_potent_and_is_structure_dependent_/1621471", "title"=>"HBD3 effect on Interferon-β response to polyI:C is potent and is structure dependent.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-08 06:39:06"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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