Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases
Publication Date
August 21, 2009
Journal
PLOS Pathogens
Authors
Marina Tiemi Shio, Stephanie C. Eisenbarth, Myriam Savaria, Adrien F. Vinet, et al
Volume
5
Issue
8
Pages
e1000559
DOI
https://dx.plos.org/10.1371/journal.ppat.1000559
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1000559
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/19696895
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722371
Europe PMC
http://europepmc.org/abstract/MED/19696895
Web of Science
000270804500014
Scopus
70049101754
Mendeley
http://www.mendeley.com/research/malarial-hemozoin-activates-nlrp3-inflammasome-through-lyn-syk-kinases
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Mendeley | Further Information

{"title"=>"Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases", "type"=>"journal", "authors"=>[{"first_name"=>"Marina", "last_name"=>"Tiemi Shio", "scopus_author_id"=>"34875770000"}, {"first_name"=>"Stephanie C.", "last_name"=>"Eisenbarth", "scopus_author_id"=>"6603458233"}, {"first_name"=>"Myriam", "last_name"=>"Savaria", "scopus_author_id"=>"34875713600"}, {"first_name"=>"Adrien F.", "last_name"=>"Vinet", "scopus_author_id"=>"25422961700"}, {"first_name"=>"Marie Josée", "last_name"=>"Bellemare", "scopus_author_id"=>"6701858569"}, {"first_name"=>"Kenneth W.", "last_name"=>"Harder", "scopus_author_id"=>"7005798852"}, {"first_name"=>"Fayyaz S.", "last_name"=>"Sutterwala", "scopus_author_id"=>"6506812310"}, {"first_name"=>"D. Scott", "last_name"=>"Bohle", "scopus_author_id"=>"7005241669"}, {"first_name"=>"Albert", "last_name"=>"Descoteaux", "scopus_author_id"=>"7003409065"}, {"first_name"=>"Richard A.", "last_name"=>"Flavell", "scopus_author_id"=>"36047925100"}, {"first_name"=>"Martin", "last_name"=>"Olivier", "scopus_author_id"=>"7101741151"}], "year"=>2009, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537366", "isbn"=>"1553-7374 (Electronic)", "pmid"=>"19696895", "scopus"=>"2-s2.0-70049101754", "pui"=>"355237394", "doi"=>"10.1371/journal.ppat.1000559", "sgr"=>"70049101754"}, "id"=>"219db999-fad6-396b-98a6-f5fd0485a8a4", "abstract"=>"The intraerythrocytic parasite Plasmodium -- the causative agent of malaria -- produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into the circulation during erythrocyte lysis. Hz is rapidly ingested by phagocytes and induces the production of several pro-inflammatory mediators such as interleukin-1beta (IL-1beta). However, the mechanism regulating Hz recognition and IL-1beta maturation has not been identified. Here, we show that Hz induces IL-1beta production. Using knockout mice, we showed that Hz-induced IL-1beta and inflammation are dependent on NOD-like receptor containing pyrin domain 3 (NLRP3), ASC and caspase-1, but not NLRC4 (NLR containing CARD domain). Furthermore, the absence of NLRP3 or IL-1beta augmented survival to malaria caused by P. chabaudi adami DS. Although much has been discovered regarding the NLRP3 inflammasome induction, the mechanism whereby this intracellular multimolecular complex is activated remains unclear. We further demonstrate, using pharmacological and genetic intervention, that the tyrosine kinases Syk and Lyn play a critical role in activation of this inflammasome. These findings not only identify one way by which the immune system is alerted to malarial infection but also are one of the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLRP3 inflammasome.", "link"=>"http://www.mendeley.com/research/malarial-hemozoin-activates-nlrp3-inflammasome-through-lyn-syk-kinases", "reader_count"=>146, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>11, "Researcher"=>36, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>41, "Student > Master"=>19, "Other"=>5, "Student > Bachelor"=>10, "Lecturer"=>2, "Professor"=>9}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>11, "Researcher"=>36, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>41, "Student > Master"=>19, "Other"=>5, "Student > Bachelor"=>10, "Lecturer"=>2, "Professor"=>9}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Engineering"=>3, "Biochemistry, Genetics and Molecular Biology"=>13, "Medicine and Dentistry"=>19, "Agricultural and Biological Sciences"=>81, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>2, "Social Sciences"=>1, "Immunology and Microbiology"=>16}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>19}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>16}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>81}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>8}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "Japan"=>1, "United Kingdom"=>1, "Portugal"=>1, "India"=>1, "Spain"=>1, "Canada"=>1, "Turkey"=>1, "Belgium"=>1, "Brazil"=>1, "France"=>1, "Australia"=>1, "Germany"=>1}, "group_count"=>2}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/887129"], "description"=>"<p>PMA-differentiated THP-1 cells (0.75×10<sup>6</sup> cells/0.5 mL) were stimulated with Hz (200 µg/mL) or MSU (100 µg/mL) and exposed to the indicated concentrations of (A) phagocytosis inhibitor cytochalasin D, (C) the ROS-scavenger N-acetyl cysteine (NAC), (D) extracellular potassium or, (F) the cathepsin B inhibitor CA-074. After six hours of incubation, supernatant (SN) and cell extracts were collected and subjected to Western blot analysis with the indicated antibodies. (B) BMDM were incubated or not with 200 µg/mL Hz (green) and stained for LAMP-1 (red) and for nucleus with DRAQ5 (blue). (E) PMA-differentiated THP-1 cells were stimulated or not with Hz (200 µg/mL) or silica (400 µg/mL) in the presence of DQ-OVA (10 µg/mL) for 30 minutes, washed and further incubated for three more hours. Green fluorescence represents cleaved OVA. Data shown are images obtained by confocal microscopy from one representative experiment of three independent experiments. Scale bars = 5 µm.</p>", "links"=>[], "tags"=>["reactive", "potassium", "efflux", "cathepsin"], "article_id"=>557578, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g004", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hemozoin_induced_IL_1_946_production_is_dependent_on_phagocytosis_reactive_oxygen_species_ROS_generation_potassium_efflux_and_cathepsin_B_/557578", "title"=>"Hemozoin-induced IL-1β production is dependent on phagocytosis, reactive oxygen species (ROS) generation, potassium efflux and cathepsin B.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:06:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/887537"], "description"=>"<p>PMA-differentiated THP-1 cells (10×10<sup>6</sup> cells per immunoprecipitation - IP) were stimulated with Hz (200 µg/mL) for the indicated time. Lysates were immunoprecipitated with a specific antibody to SYK or matched isotype control and samples were subjected to (A left panel) silver staining or (A right panel) to Western blot analysis to phosphorylated tyrosine residues (pY). Squares in A left panel represent the bands excised and analyzed with LC-MS/MS. (B) Samples from IP with a specific antibody to Syk, ASC or matched isotype control and samples were subjected to Western blot (WB) analysis with specific antibody for Syk, ASC or NLRP3. Numbers to the left of blots represent protein size in kDa. Data show one experiment representative of three independent experiments.</p>", "links"=>[], "tags"=>["complexes", "inflammasome"], "article_id"=>557987, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g008", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Syk_complexes_with_inflammasome_proteins_/557987", "title"=>"Syk complexes with inflammasome proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:13:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/886974"], "description"=>"<p>Wild type (WT), NLRP3- or IL-1β-deficient mice were infected with <i>Plasmodium chabaudi adami</i> strain DS and after the indicated time, the mouse body temperature (A and B), parasitemia (C and D), and survival of mice (E and F) were monitored. IL-1β was measured in serum collected before death (G), dashed line represents ELISA detection limit. Statistical differences (A, B and G) were estimated using <i>t</i> test. Statistical significances between survival curves were determined using the Mantel–Haenszel test. *<i>p</i><0.05. Results from a representative infection experiment (n = 5–8) are shown.</p>", "links"=>[], "tags"=>["mice", "malaria", "reduced"], "article_id"=>557425, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NLPR3_and_IL_1_946_deficient_mice_show_increased_survival_to_malaria_infection_and_reduced_fever_/557425", "title"=>"NLPR3- and IL-1β-deficient mice show increased survival to malaria infection and reduced fever.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:03:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/439554", "https://ndownloader.figshare.com/files/439570", "https://ndownloader.figshare.com/files/439576", "https://ndownloader.figshare.com/files/439586", "https://ndownloader.figshare.com/files/439589"], "description"=>"<div><p>The intraerythrocytic parasite <em>Plasmodium—</em>the causative agent of malaria—produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into the circulation during erythrocyte lysis. Hz is rapidly ingested by phagocytes and induces the production of several pro-inflammatory mediators such as interleukin-1β (IL-1β). However, the mechanism regulating Hz recognition and IL-1β maturation has not been identified. Here, we show that Hz induces IL-1β production. Using knockout mice, we showed that Hz-induced IL-1β and inflammation are dependent on NOD-like receptor containing pyrin domain 3 (NLRP3), ASC and caspase-1, but not NLRC4 (NLR containing CARD domain). Furthermore, the absence of NLRP3 or IL-1β augmented survival to malaria caused by <em>P. chabaudi adami</em> DS. Although much has been discovered regarding the NLRP3 inflammasome induction, the mechanism whereby this intracellular multimolecular complex is activated remains unclear. We further demonstrate, using pharmacological and genetic intervention, that the tyrosine kinases Syk and Lyn play a critical role in activation of this inflammasome. These findings not only identify one way by which the immune system is alerted to malarial infection but also are one of the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLRP3 inflammasome.</p></div>", "links"=>[], "tags"=>["malarial", "hemozoin", "activates", "nlrp3", "inflammasome", "lyn", "syk", "kinases"], "article_id"=>146658, "categories"=>["Cancer", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000559.s001", "https://dx.doi.org/10.1371/journal.ppat.1000559.s002", "https://dx.doi.org/10.1371/journal.ppat.1000559.s003", "https://dx.doi.org/10.1371/journal.ppat.1000559.s004", "https://dx.doi.org/10.1371/journal.ppat.1000559.s005"], "stats"=>{"downloads"=>2, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Malarial_Hemozoin_Activates_the_NLRP3_Inflammasome_through_Lyn_and_Syk_Kinases/146658", "title"=>"Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-08-21 01:50:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/887646"], "description"=>"<p>PMA-differentiated THP-1 cells (0.75×10<sup>6</sup> cells/0.5 mL) were stimulated with Hz (200 µg/mL), MSU (100 µg/mL) or silica (Sil, 400 µg/mL). After different times of incubation, supernatant (SN) and cell extracts were collected and subjected to Western blot analysis with the indicated antibodies (A). PMA-differentiated THP-1 cells (0.2×10<sup>6</sup> cells/0.5 mL) were pre-treated (30 min) with 5 µM of piceatannol and incubated or not with 200 µg/mL Hz (green) and cathepsin B activity was detected using a red fluorescence substrate of cathepsin B. Data shown are images obtained by confocal microscopy from one representative experiment of three independent experiments. Scale bars = 5 µm (B).</p>", "links"=>[], "tags"=>["cathepsin", "regulated"], "article_id"=>558097, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g009", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hz_activated_Cathepsin_B_is_regulated_by_Syk_/558097", "title"=>"Hz-activated Cathepsin B is regulated by Syk.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:14:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/887235"], "description"=>"<p>PMA-differentiated THP-1 cells (0.75×10<sup>6</sup> cells/0.5 mL or 10×10<sup>6</sup> cell per immunoprecipitation - IP) were stimulated with Hz (200 µg/mL) or MSU (100 µg/mL) for the indicated time or 30 min if not indicated and (A) cell lysates or (B) samples from IP with a specific antibody to Syk or a matched isotype control were subjected to western blot analysis to phosphorylated tyrosine residues (pY). (C) Cells were pre-treated with the Src inhibitor PP2. (D) BMDM (1.5×10<sup>6</sup> cell/mL) from wild type (WT) or Lyn-deficient mice were pretreated for three hours with LPS (100 ng/mL), washed and treated or not with Hz (200 µg/mL) or MSU (100 µg/mL) for 30 minutes. IP samples or total cell lysates were subjected to Western blot analysis with the indicated antibodies. Numbers to the left of blots represent protein size in kDa.</p>", "links"=>[], "tags"=>["induces", "syk", "phosphorylation", "src"], "article_id"=>557680, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g005", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hz_induces_Syk_phosphorylation_dependent_on_Src_kinases_/557680", "title"=>"Hz induces Syk phosphorylation dependent on Src kinases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:08:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/887455"], "description"=>"<p>PMA-differentiated THP-1 cells (0.75×10<sup>6</sup> cells/0.5 mL) were pretreated with: (A) PI3K inhibitor – wortmannin, (B and D) p38 inhibitor - SB 203580, or (E) ERK inhibitor - apigenin followed by Hz (200 µg/mL) stimulation for six hours (IL-1β) or 30 minutes (pp38) or the indicated time (C). Supernatant (SN) and cell lysates were subjected to Western blot analysis with the indicated antibodies. Data show one experiment representative of two to five independent experiments.</p>", "links"=>[], "tags"=>["kinases", "hemozoin-induced"], "article_id"=>557902, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g007", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_role_of_other_kinases_in_hemozoin_induced_IL_1_946_/557902", "title"=>"The role of other kinases in hemozoin-induced IL-1β.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:11:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/886704"], "description"=>"<p>(A) PMA-differentiated THP-1 cells (0.75×10<sup>6</sup> cells/0.5 mL) were stimulated with the indicated concentration of hemozoin (Hz) or Monosodium Urate (MSU) and (B) pre-treated or not with the HSP-90 inhibitor geldanamycin D or (C) the caspase-1 specific inhibitor Y-VAD-FMK or the broad caspase inhibitor Z-VAD-CHO. (D) Bone marrow derived macrophages – BMDM - (1.5×10<sup>6</sup>/mL) from either caspase-1-deficient or wild type (WT) mice were pre-treated with LPS (100 ng/mL) for three hours, washed and incubated with Hz (200 µg/mL) or MSU (100 µg/mL). After six hours of incubation, supernatant (SN) and cell extracts were collected and subjected to Western blot analysis with the indicated antibodies. Data show one experiment representative of three to five independent experiments.</p>", "links"=>[], "tags"=>["induces", "maturation", "secretion", "hsp-90", "caspase-1"], "article_id"=>557145, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hemozoin_induces_IL_1_946_maturation_and_secretion_and_is_dependent_on_HSP_90_stability_and_caspase_1_activation_/557145", "title"=>"Hemozoin induces IL-1β maturation and secretion and is dependent on HSP-90 stability and caspase-1 activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 01:59:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/887358"], "description"=>"<p>PMA-differentiated THP-1 cells (0.75×10<sup>6</sup> cells/0.5 mL) were pretreated with either the SYK inhibitor piceatannol (A) or the Src inhibitor PP2 (B). BMDM (1.5×10<sup>6</sup> cell/mL) from wild type (WT) or Lyn-deficient mice were pretreated for three hours with LPS (100 ng/mL), washed and treated or not with Hz (200 µg/mL) or MSU (100 µg/mL) for six hours (C). Supernatant (SN) or total cell lysates were subjected to Western blot analysis with the indicated antibodies. Numbers to the left of blots represent protein size in kDa. (C) Bars show mean+/−S.E.M. of densitometry of three independent experiments. *<i>p</i><0.05 comparing Lyn-deficient <i>vs.</i> WT mice. BMDM were treated as described in the legend of <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000559#ppat-1000559-g002\" target=\"_blank\">Fig. 2A</a> were stimulated for 30 minutes and data show one experiment representative of three to five independent experiments (D).</p>", "links"=>[], "tags"=>["src", "kinases", "induced"], "article_id"=>557802, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g006", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Syk_and_Src_kinases_regulate_IL_1_946_production_induced_by_hemozoin_/557802", "title"=>"Syk and Src kinases regulate IL-1β production induced by hemozoin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:10:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/886876"], "description"=>"<p>(A) BMDM (1.5×10<sup>6</sup> cells/mL) from wild type (WT), NLRP3-, ASC- or NLRC4-deficient mice were pretreated for three hours with LPS (100 ng/mL) for three hours, washed and stimulated with Hz (200 µg/mL) or MSU (100 µg/mL) where indicated. After six hours, supernatant (SN) and cell extracts were collected and subjected to Western blot analysis with the indicated antibodies. ND: not determined. (B) WT and ASC-deficient or (C) WT, NLRP3- and NLRC4-deficient or (D) WT and IL-1β-deficient mice were injected with 800 µg of hemozoin intraperitoneally in 1 mL PBS. After six hours, peritoneal cells were harvested, neutrophils were counted per total cell numbers and basal neutrophil influx (in PBS injected mice) was subtracted to determine total neutrophilic peritoneal recruitment. Data show one experiment representative of three independent experiments. Bars show mean+/−S.E.M., n = 4–6 mice/group. Unpaired Student's t-test was used to calculate P values (*<i>p</i><0.05).</p>", "links"=>[], "tags"=>["neutrophil", "recruitment", "induced", "hemozoin", "requires", "asc"], "article_id"=>557321, "categories"=>["Infectious Diseases", "Immunology", "Physics", "Cell Biology"], "users"=>["Marina Tiemi Shio", "Stephanie C. Eisenbarth", "Myriam Savaria", "Adrien F. Vinet", "Marie-Josée Bellemare", "Kenneth W. Harder", "Fayyaz S. Sutterwala", "D. Scott Bohle", "Albert Descoteaux", "Richard A. Flavell", "Martin Olivier"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000559.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_1_946_production_and_neutrophil_recruitment_induced_by_hemozoin_requires_NLRP3_ASC_and_IL_1_946_but_not_NLRC4_/557321", "title"=>"IL-1β production and neutrophil recruitment induced by hemozoin requires NLRP3, ASC and IL-1β but not NLRC4.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-21 02:02:01"}

PMC Usage Stats | Further Information

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Relative Metric

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