Porphyromonas gingivalis Regulates TREM-1 in Human Polymorphonuclear Neutrophils via Its Gingipains
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{"title"=>"Porphyromonas gingivalis Regulates TREM-1 in Human Polymorphonuclear Neutrophils via Its Gingipains", "type"=>"journal", "authors"=>[{"first_name"=>"Nagihan", "last_name"=>"Bostanci", "scopus_author_id"=>"14059543900"}, {"first_name"=>"Thomas", "last_name"=>"Thurnheer", "scopus_author_id"=>"6603044428"}, {"first_name"=>"Joseph", "last_name"=>"Aduse-Opoku", "scopus_author_id"=>"6701655088"}, {"first_name"=>"Michael A.", "last_name"=>"Curtis", "scopus_author_id"=>"7201873916"}, {"first_name"=>"Annelies S.", "last_name"=>"Zinkernagel", "scopus_author_id"=>"15129227000"}, {"first_name"=>"Georgios N.", "last_name"=>"Belibasakis", "scopus_author_id"=>"6602710187"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84885079167", "pmid"=>"24124513", "sgr"=>"84885079167", "doi"=>"10.1371/journal.pone.0075784", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"369964524"}, "id"=>"be461c2f-cc1e-3daa-9849-1034b2c2acba", "abstract"=>"The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, with the capacity to amplify pro-inflammatory cytokine production and regulate apoptosis. Polymorphonuclear neutrophils (PMNs) are the first line of defence against infection, and a major source of TREM-1. Porphyromonas gingivalis is a Gram-negative anaerobe highly implicated in the inflammatory processes governing periodontal disease, which is characterized by the destruction of the tooth-supporting tissues. It expresses a number of virulence factors, including the cysteine proteinases (or gingipains). The aim of this in vitro study was to investigate the effect of P. gingivalis on TREM-1 expression and production by primary human PMNs, and to evaluate the role of its gingipains in this process. After 4 h of challenge, P. gingivalis enhanced TREM-1 expression as identified by quantitative real-time PCR. This was followed by an increase in soluble (s)TREM-1 secretion over a period of 18 h, as determined by ELISA. At this time-point, the P. gingivalis-challenged PMNs exhibited diminished TREM-1 cell-membrane staining, as identified by flow cytometry and confocal laser scanning microscopy. Furthermore engagement of TREM-1, by means of anti-TREM-1 antibodies, enhanced the capacity of P. gingivalis to stimulate interleukin (IL)-8 production. Conversely, antagonism of TREM-1 using a synthetic peptide resulted in reduction of IL-8 secretion. Using isogenic P. gingivalis mutant strains, we identified the Arg-gingipain to be responsible for shedding of sTREM-1 from the PMN surface, whereas the Lys-gingipain had the capacity to degrade TREM-1. In conclusion, the differential regulation of TREM-1 by the P. gingivalis gingipains may present a novel mechanism by which P. gingivalis manipulates the host innate immune response helping to establish chronic periodontal inflammation.", "link"=>"http://www.mendeley.com/research/porphyromonas-gingivalis-regulates-trem1-human-polymorphonuclear-neutrophils-via-gingipains", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>7, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>3}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1225619"], "description"=>"<p>TREM-1-associated fluorescence on the cell surface was detected by staining with anti-TREM-1-FITC. Results from one experiment are presented (red: unstained cells, dark blue: unchallenged control, green: cells challenged with <i>P. gingivalis</i> W50 MOI 1, orange: cells challenged with <i>P. gingivalis</i> W50 MOI 10, light blue: cells challenged with <i>P. gingivalis</i> W50 MOI 100).</p>", "links"=>[], "tags"=>["cytometic", "pmns", "challenged", "w50"], "article_id"=>815390, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flow_cytometic_analysis_of_PMNs_challenged_for_4_P_gingivalis_W50_MOI_/815390", "title"=>"Flow cytometic analysis of PMNs challenged for 4<i>P. gingivalis</i> W50 MOI.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1225627"], "description"=>"<p>Recombinant human sTREM-1 (2000 pg/ml) was spiked into cell culture media in absence or presence of <i>P. gingivalis</i> W50 wild-type, Arg-gingipain E8 or Lys-gingipain K1A mutant strain (MOI 100) for 18 h. Bars represent mean values ± standard errors of mean (SEM) from one experiment in triplicate. The asterisk represents statistically significant difference between the control and the <i>P. gingivalis</i>-challenged groups.</p>", "links"=>[], "tags"=>["gingipains", "strem-1"], "article_id"=>815398, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g007", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_P_gingivalis_gingipains_on_sTREM_1_degradation_/815398", "title"=>"Effect of <i>P. gingivalis</i> gingipains on sTREM-1 degradation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1225623"], "description"=>"<p>PMNs were exposed to <i>P. gingivalis</i> W50, the Arg-gingipain mutant E8 or the Lys-gingipain mutant K1A strain (MOI 100). After 4 h, the gene expression levels of TREM-1 were measured by qPCR analysis, normalized against the expression levels of the house-keeping gene. The results are expressed as the 2<sup>−ΔCT</sup> formula (A). After 18 h, secretion of sTREM-1 by PMNs into the culture supernatants was measured by ELISA (B). Bars represent mean values ± standard errors of mean (SEM) from three independent experiments. The asterisk represents statistically significant difference between the <i>P. gingivalis</i>-challenged and control groups.</p>", "links"=>[], "tags"=>["gingipains", "trem-1"], "article_id"=>815394, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g005", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Involvement_of_gingipains_in_TREM_1_gene_expression_and_secretion_/815394", "title"=>"Involvement of gingipains in TREM-1 gene expression and secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1225617"], "description"=>"<p>PMNs were exposed to <i>P. gingivalis</i> W50 at MOI 1, 10 or 100. After 4 h, the gene expression levels of TREM-1 were measured by qPCR analysis, normalized against the expression levels of the house-keeping gene. The results are expressed as the 2<sup>−ΔCT</sup> formula (A). After 18 h, secretion of sTREM-1 by PMNs into the culture supernatants were measured by ELISA (B). Bars represent mean values ± standard errors of mean (SEM) from three independent experiments. The asterisk represents statistically significant difference between the <i>P. gingivalis</i>-challenged and control groups.</p>", "links"=>[], "tags"=>["trem-1", "strem-1", "secretion"], "article_id"=>815388, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_TREM_1_gene_expression_and_sTREM_1_secretion_in_PMNs_in_response_to_P_gingivalis_/815388", "title"=>"Induction of TREM-1 gene expression and sTREM-1 secretion in PMNs, in response to <i>P. gingivalis</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1225626"], "description"=>"<p>TREM-1 on the cell surface was visualized using anti-TREM-1-FITC (green), and the cell nuclei appear blue due to counter-staining of the DNA with DAPI. Bacteria were stained by FISH with P-Pging1006-2-Cy3 probe and Cy5-labelled universal bacterial probe EUB338. Control cells, only DAPI stained (A); control cells, stained by both DAPI and anti-TREM-1-FITC (B); cells infected with <i>P. gingivalis</i> W50 (red) (C); cells infected with <i>P. gingivalis</i> K1A (red) (D); cells infected with <i>P. gingivalis</i> E8 (E) (Scales = 15 µm).</p>", "links"=>[], "tags"=>["confocal", "scanning", "microscopy", "images", "pmn", "cells", "infected", "w50", "arg-gingipain", "e8", "lys-gingipain", "k1a", "mutant"], "article_id"=>815397, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g006", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_confocal_laser_scanning_microscopy_CLSM_images_of_PMN_cells_infected_with_P_gingivalis_W50_wild_type_or_the_Arg_gingipain_E8_and_Lys_gingipain_K1A_mutant_strains_/815397", "title"=>"Representative confocal laser scanning microscopy (CLSM) images of PMN cells infected with <i>P. gingivalis</i> W50 wild-type, or the Arg-gingipain E8 and Lys-gingipain K1A mutant strains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1225622"], "description"=>"<p>PMNs were cultured in 96-well plates pre-coated with anti-human TREM-1, or matching IgG<sub>1</sub> isotype control, or in the presence of LP17 (100 ng/ml) and exposed to <i>P. gingivalis</i> MOI 100 for 18 h. Upon completion of the experiments, the cell-free culture supernatants were collected and the concentrations of IL-8 were measured by ELISA. Bars represent mean values ± standard errors of mean (SEM) from three independent experiments. The asterisk represents statistically significant difference between the control and the corresponding <i>P. gingivalis</i>-challenged groups.</p>", "links"=>[], "tags"=>["antagonism", "trem-1", "il-8", "stimulating-responses"], "article_id"=>815393, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g004", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Engagement_and_antagonism_of_TREM_1_in_IL_8_stimulating_responses_by_P_gingivalis_/815393", "title"=>"Engagement and antagonism of TREM-1 in IL-8 stimulating-responses by <i>P. gingivalis</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1225620"], "description"=>"<p>TREM-1 on the cell surface was visualized using anti-TREM-1-FITC (green), and t<a href=\"http://h\" target=\"_blank\">h</a>e cell nuclei appear blue due to counter-staining of the DNA with DAPI. Bacteria were stained by FISH with P-Pging1006-Cy3 and universal bacterial probe EUB338-Cy5. Control cells, only DAPI stained (green appears due to autofluorescence) (A), Control cells, stained by both DAPI and anti-TREM-1-FITC (B); Cells infected with <i>P. gingivalis</i> W50 (yellow) indicated by arrow, stained by both DAPI and anti-TREM-1-FITC (C). Scales = 10 µm (A, B) and 5 µm (C).</p>", "links"=>[], "tags"=>["confocal", "scanning", "microscopy", "images", "pmns", "infected", "moi", "100", "18"], "article_id"=>815391, "categories"=>["Biological Sciences"], "users"=>["Nagihan Bostanci", "Thomas Thurnheer", "Joseph Aduse-Opoku", "Michael A. Curtis", "Annelies S. Zinkernagel", "Georgios N. Belibasakis"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0075784.g003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_confocal_laser_scanning_microscopy_CLSM_images_of_PMNs_infected_with_P_gingivalis_MOI_100_for_18_h_/815391", "title"=>"Representative confocal laser scanning microscopy (CLSM) images of PMNs infected with <i>P. gingivalis</i> MOI 100 for 18 h.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-04 02:31:01"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
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Relative Metric

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