CD44-Deficiency Attenuates the Immunologic Responses to LPS and Delays the Onset of Endotoxic Shock-Induced Renal Inflammation and Dysfunction
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{"title"=>"CD44-deficiency attenuates the immunologic responses to LPS and delays the onset of endotoxic shock-induced renal inflammation and dysfunction", "type"=>"journal", "authors"=>[{"first_name"=>"Elena", "last_name"=>"Rampanelli", "scopus_author_id"=>"36343924900"}, {"first_name"=>"Mark C.", "last_name"=>"Dessing", "scopus_author_id"=>"8882234800"}, {"first_name"=>"Nike", "last_name"=>"Claessen", "scopus_author_id"=>"6602077013"}, {"first_name"=>"Gwendoline J.D.", "last_name"=>"Teske", "scopus_author_id"=>"8843381500"}, {"first_name"=>"Sander P.J.", "last_name"=>"Joosten", "scopus_author_id"=>"14028467300"}, {"first_name"=>"Steven T.", "last_name"=>"Pals", "scopus_author_id"=>"7005446990"}, {"first_name"=>"Jaklien C.", "last_name"=>"Leemans", "scopus_author_id"=>"7004426357"}, {"first_name"=>"Sandrine", "last_name"=>"Florquin", "scopus_author_id"=>"56238343600"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0084479", "pui"=>"372292866", "sgr"=>"84893434475", "scopus"=>"2-s2.0-84893434475", "pmid"=>"24376813", "issn"=>"19326203"}, "id"=>"24471d8b-3f35-3828-9253-25eaedc427cf", "abstract"=>"Acute kidney injury (AKI) is a common complication during systemic inflammatory response syndrome (SIRS), a potentially deadly clinical condition characterized by whole-body inflammatory state and organ dysfunction. CD44 is a ubiquitously expressed cell-surface transmembrane receptor with multiple functions in inflammatory processes, including sterile renal inflammation. The present study aimed to assess the role of CD44 in endotoxic shock-induced kidney inflammation and dysfunction by using CD44 KO and WT mice exposed intraperitoneally to LPS for 2, 4, and 24 hours . Upon LPS administration, CD44 expression in WT kidneys was augmented at all time-points. At 2 and 4 hours, CD44 KO animals showed a preserved renal function in comparison to WT mice. In absence of CD44, the pro-inflammatory cytokine levels in plasma and kidneys were lower, while renal expression of the anti-inflammatory cytokine IL-10 was higher. The cytokine levels were associated with decreased leukocyte influx and endothelial activation in CD44 KO kidneys. Furthermore, in vitro assays demonstrated a role of CD44 in enhancing macrophage cytokine responses to LPS and leukocyte migration. In conclusion, our study demonstrates that lack of CD44 impairs the early pro-inflammatory cytokine response to LPS, diminishes leukocyte migration/chemotaxis and endothelial activation, hence, delays endotoxic shock-induced AKI.", "link"=>"http://www.mendeley.com/research/cd44deficiency-attenuates-immunologic-responses-lps-delays-onset-endotoxic-shockinduced-renal-inflam", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1327784"], "description"=>"<p>Expression (pg/mg proteins) of (<b>A</b>) MCP-1, (<b>B</b>) IL-1β, (<b>C</b>) TNF-α, (<b>D</b>) IL-6 and (<b>E</b>) IL-10 in kidneys of WT (white bars) and CD44 KO (black bars) mice measured by ELISA. Data shown as mean <u>+</u> SEM, n=8, *=p<0.05.</p>", "links"=>[], "tags"=>[], "article_id"=>886089, "categories"=>["Biological Sciences"], "users"=>["Elena Rampanelli", "Mark C. Dessing", "Nike Claessen", "Gwendoline J. D. Teske", "Sander P. J. Joosten", "Steven T. Pals", "Jaklien C. Leemans", "Sandrine Florquin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0084479.g004", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokines_in_the_kidneys_/886089", "title"=>"Cytokines in the kidneys.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-23 04:23:22"}
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  • {"files"=>["https://ndownloader.figshare.com/files/1327786"], "description"=>"<p>(<b>A</b>) iNOS expression detected by immunostaining in paraffin renal sections of WT (white bars) and CD44 KO (black bars); quantification shown as positive area percentage of total area. (<b>B</b>) Q-PCR analysis for renal expression of VCAM-1; data normalized for TBP expression levels. (<b>C</b>) Digital analysis of VCAM-1 protein expression 2 hours after LPS injection, assessed by immunohistochemistry on frozen renal sections. Results expressed as positive area percentage of total area. Mean <u>+</u> SEM, n=8, *=p<0.05 **=p<0.01, WT vs CD44 KO; #=p<0.05, ##=P<0.01, vs sham.</p>", "links"=>[], "tags"=>["endothelial"], "article_id"=>886091, "categories"=>["Biological Sciences"], "users"=>["Elena Rampanelli", "Mark C. Dessing", "Nike Claessen", "Gwendoline J. D. Teske", "Sander P. J. Joosten", "Steven T. Pals", "Jaklien C. Leemans", "Sandrine Florquin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0084479.g006", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Renal_endothelial_activation_/886091", "title"=>"Renal endothelial activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-23 04:23:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1327787"], "description"=>"<p><i>In </i><i>vitro</i> LPS (100ng/ml) stimulation of WT (white bars) and CD44 KO (black bars) bone marrow-derived macrophages (BMM) for 4 and 24 hours. Secretion levels (pg/ml) of (<b>A</b>) TNF-α and (<b>B</b>) IL-6 detected by ELISA. (<b>C</b>) Gene expression of IL-1β and (<b>D</b>) IFNβ normalized for TBP transcript levels, assessed by Q-PCR. (<b>E</b>) ELISA measurement of IL-10 supernatant concentration (pg/ml). Mean <u>+</u> SEM, n=10, *=p<0.05, ***=p<0.001. (<b>F</b>) WB assay of cell lysates from WT and CD44 KO BMM for detection of cytoplasmatic phosphorylated (p)-IκBα and nuclear p65. β-actin or LaminA/C used as loading controls. Fold-increase in protein expression in respect to control is indicated. </p>", "links"=>[], "tags"=>["lps"], "article_id"=>886092, "categories"=>["Biological Sciences"], "users"=>["Elena Rampanelli", "Mark C. Dessing", "Nike Claessen", "Gwendoline J. D. Teske", "Sander P. J. Joosten", "Steven T. Pals", "Jaklien C. Leemans", "Sandrine Florquin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0084479.g007", "stats"=>{"downloads"=>0, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Macrophage_response_to_LPS_in_presence_absence_of_CD44_/886092", "title"=>"Macrophage response to LPS in presence/absence of CD44.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-23 04:23:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1327790"], "description"=>"<p><i>In </i><i>vitro</i> LPS (100ng/ml) stimulation of WT (white bars) and CD44 KO (black bars) BMM for 4 hours after CD44-ligation. (<b>A</b>) ELISA for detection of TNF-α in supernatants; data shown as fold-increase compared to LPS-stimulated BMM. (<b>B</b>) TNF-α levels (pg/ml) in presence or not of 10µM SB203580, 10mM 3-MA, or 0.5ug/ml Cli095 (ELISA). Mean <u>+</u> SEM, n=6, *=p<0.05, WT vs CD44 KO; #=p<0.05, ##=p<0.01, vs WT+LPS (no inhibitors); ^^=p<0.01, vs CD44 KO+LPS (no inhibitors).</p>", "links"=>[], "tags"=>["macrophages", "cd44-ligation", "inhibitors"], "article_id"=>886095, "categories"=>["Biological Sciences"], "users"=>["Elena Rampanelli", "Mark C. Dessing", "Nike Claessen", "Gwendoline J. D. Teske", "Sander P. J. Joosten", "Steven T. Pals", "Jaklien C. Leemans", "Sandrine Florquin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0084479.g008", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LPS_challenged_macrophages_after_CD44_ligation_and_inhibitors_pre_treatment_/886095", "title"=>"LPS-challenged macrophages after CD44-ligation and inhibitors pre-treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-23 04:23:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1327792"], "description"=>"<p>Transwell migration assay of (<b>A</b>) monocytes and (<b>B</b>) granulocytes from WT (white bars) and CD44 KO (black bars) blood. Immunofluorescent staining for flow cytometric analysis of (<b>A</b>) CD11b and (<b>B</b>) Ly6G after 24 hours culture in Transwell plate with or without 200ng/ml MIP-2 and MCP-1 in the lower chamber. Data expressed as percent cells in the lower chamber of the total number of cells. Mean <u>+</u> SEM, n=3, *=p<0.05, WT vs CD44 KO; ###=p<0.001, vs control. </p>", "links"=>[], "tags"=>["leukocytes"], "article_id"=>886097, "categories"=>["Biological Sciences"], "users"=>["Elena Rampanelli", "Mark C. Dessing", "Nike Claessen", "Gwendoline J. D. Teske", "Sander P. J. Joosten", "Steven T. Pals", "Jaklien C. Leemans", "Sandrine Florquin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0084479.g009", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Migratory_ability_of_blood_leukocytes_in_absence_of_CD44_/886097", "title"=>"Migratory ability of blood leukocytes in absence of CD44.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-23 04:23:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1327798"], "description"=>"<div><p>Acute kidney injury (AKI) is a common complication during systemic inflammatory response syndrome (SIRS), a potentially deadly clinical condition characterized by whole-body inflammatory state and organ dysfunction. CD44 is a ubiquitously expressed cell-surface transmembrane receptor with multiple functions in inflammatory processes, including sterile renal inflammation. The present study aimed to assess the role of CD44 in endotoxic shock-induced kidney inflammation and dysfunction by using CD44 KO and WT mice exposed intraperitoneally to LPS for 2, 4, and 24 hours . Upon LPS administration, CD44 expression in WT kidneys was augmented at all time-points. At 2 and 4 hours, CD44 KO animals showed a preserved renal function in comparison to WT mice. In absence of CD44, the pro-inflammatory cytokine levels in plasma and kidneys were lower, while renal expression of the anti-inflammatory cytokine IL-10 was higher. The cytokine levels were associated with decreased leukocyte influx and endothelial activation in CD44 KO kidneys. Furthermore, <i>in vitro</i> assays demonstrated a role of CD44 in enhancing macrophage cytokine responses to LPS and leukocyte migration. In conclusion, our study demonstrates that lack of CD44 impairs the early pro-inflammatory cytokine response to LPS, diminishes leukocyte migration/chemotaxis and endothelial activation, hence, delays endotoxic shock-induced AKI. </p> </div>", "links"=>[], "tags"=>["attenuates", "immunologic", "responses", "lps", "delays", "onset", "endotoxic", "shock-induced", "renal", "inflammation"], "article_id"=>886103, "categories"=>["Biological Sciences"], "users"=>["Elena Rampanelli", "Mark C. Dessing", "Nike Claessen", "Gwendoline J. D. Teske", "Sander P. J. Joosten", "Steven T. Pals", "Jaklien C. Leemans", "Sandrine Florquin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0084479", "stats"=>{"downloads"=>3, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD44_Deficiency_Attenuates_the_Immunologic_Responses_to_LPS_and_Delays_the_Onset_of_Endotoxic_Shock_Induced_Renal_Inflammation_and_Dysfunction_/886103", "title"=>"CD44-Deficiency Attenuates the Immunologic Responses to LPS and Delays the Onset of Endotoxic Shock-Induced Renal Inflammation and Dysfunction", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-23 04:23:22"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"10", "full-text"=>"15", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
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  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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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/Immunology", "average_usage"=>[266, 466, 591, 701, 799, 887, 982, 1067, 1155, 1237, 1317, 1395, 1458]}, {"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/Pathology and laboratory medicine", "average_usage"=>[267, 466, 592, 709, 806, 901, 989, 1075, 1162, 1254, 1342, 1424, 1486]}]}
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