p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans
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{"title"=>"p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans", "type"=>"journal", "authors"=>[{"first_name"=>"Emily R.", "last_name"=>"Troemel", "scopus_author_id"=>"6602655588"}, {"first_name"=>"Stephanie W.", "last_name"=>"Chu", "scopus_author_id"=>"34975222100"}, {"first_name"=>"Valerie", "last_name"=>"Reinke", "scopus_author_id"=>"6602464881"}, {"first_name"=>"Siu Sylvia", "last_name"=>"Lee", "scopus_author_id"=>"55665477900"}, {"first_name"=>"Frederick M.", "last_name"=>"Ausubel", "scopus_author_id"=>"35479582900"}, {"first_name"=>"Dennis H.", "last_name"=>"Kim", "scopus_author_id"=>"55944791000"}], "year"=>2006, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"44813572", "pmid"=>"17096597", "doi"=>"10.1371/journal.pgen.0020183", "scopus"=>"2-s2.0-33751382748", "isbn"=>"1553-7404 (Electronic)", "sgr"=>"33751382748", "issn"=>"15537390"}, "id"=>"289704d7-2137-370b-b83c-64435cac6852", "abstract"=>"The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2-DAF-16 insulin signaling pathway control Caenorhabditis elegans intestinal innate immunity. pmk-1 loss-of-function mutants have enhanced sensitivity to pathogens, while daf-2 loss-of-function mutants have enhanced resistance to pathogens that requires upregulation of the DAF-16 transcription factor. We used genetic analysis to show that the pathogen resistance of daf-2 mutants also requires PMK-1. However, genome-wide microarray analysis indicated that there was essentially no overlap between genes positively regulated by PMK-1 and DAF-16, suggesting that they form parallel pathways to promote immunity. We found that PMK-1 controls expression of candidate secreted antimicrobials, including C-type lectins, ShK toxins, and CUB-like genes. Microarray analysis demonstrated that 25% of PMK-1 positively regulated genes are induced by Pseudomonas aeruginosa infection. Using quantitative PCR, we showed that PMK-1 regulates both basal and infection-induced expression of pathogen response genes, while DAF-16 does not. Finally, we used genetic analysis to show that PMK-1 contributes to the enhanced longevity of daf-2 mutants. We propose that the PMK-1 pathway is a specific, indispensable immunity pathway that mediates expression of secreted immune response genes, while the DAF-2-DAF-16 pathway appears to regulate immunity as part of a more general stress response. The contribution of the PMK-1 pathway to the enhanced lifespan of daf-2 mutants suggests that innate immunity is an important determinant of longevity.", "link"=>"http://www.mendeley.com/research/p38-mapk-regulates-expression-immune-response-genes-contributes-longevity-c-elegans-10", "reader_count"=>167, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>8, "Researcher"=>41, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>54, "Student > Postgraduate"=>5, "Other"=>8, "Student > Master"=>21, "Student > Bachelor"=>24, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>8, "Researcher"=>41, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>54, "Student > Postgraduate"=>5, "Other"=>8, "Student > Master"=>21, "Student > Bachelor"=>24, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Environmental Science"=>4, "Biochemistry, Genetics and Molecular Biology"=>14, "Agricultural and Biological Sciences"=>134, "Medicine and Dentistry"=>5, "Design"=>1, "Sports and Recreations"=>1, "Physics and Astronomy"=>1, "Chemistry"=>3, "Social Sciences"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>134}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Environmental Science"=>{"Environmental Science"=>4}}, "reader_count_by_country"=>{"Greece"=>1, "Canada"=>1, "Netherlands"=>1, "United States"=>10, "Switzerland"=>1, "Germany"=>1, "India"=>2}, "group_count"=>2}

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  • {"files"=>["https://ndownloader.figshare.com/files/955568"], "description"=>"<div><p>(A) PA14 slow killing assay comparing survival of\n\t\t\t\t\t\t\t<i>fer-15;fem-1</i> young adult animals on\n\t\t\t\t\t\t\t<i>gacA</i> and wild-type PA14. Animals were raised in the\n\t\t\t\t\t\t\tsame way as for harvest for microarrays.</p>\n\t\t\t\t\t\t<p>(B) Intensity plot of genes regulated by PA14 versus OP50 at 4 h.\n\t\t\t\t\t\t\tSequences colored red are considered upregulated by PA14 and sequences\n\t\t\t\t\t\t\tcolored green are considered downregulated by wild-type PA14 (using\n\t\t\t\t\t\t\tResolver; <i>p</i> <0.01). Diagonal lines delineate a\n\t\t\t\t\t\t\t2-fold change. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020183#pgen-0020183-st004\" target=\"_blank\">Table S4</a> for a complete list of\n\t\t\t\t\t\t\tgenes differentially expressed between PA14 and OP50.</p>\n\t\t\t\t\t\t<p>(C) Venn diagram of overlap between genes induced in PA14 versus OP50 at\n\t\t\t\t\t\t\t4 h comparison and PA14 versus <i>gacA</i> at 4 h comparison.</p>\n\t\t\t\t\t\t<p>(D) Pie chart of gene classes induced by PA14 versus OP50. The genes (59)\n\t\t\t\t\t\t\tthat are upregulated greater than 5-fold are represented.</p></div>", "links"=>[], "tags"=>["genes"], "article_id"=>625851, "categories"=>["Genetics", "Immunology", "Infectious Diseases"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0020183.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_P__aeruginosa_Induces_Expression_of_Genes_in_Similar_Gene_Classes_as_PMK_1_8211_Induced_Genes_/625851", "title"=>"P.\n\t\t\t\t\t\t\taeruginosa Induces Expression of Genes in Similar Gene\n\t\t\t\t\t\t\tClasses as PMK-1–Induced Genes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:06:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/955408"], "description"=>"<div><p>(A) <i>pmk-1(km25)</i> suppresses <i>daf-2(e1368)</i>\n\t\t\t\t\t\t\tenhanced pathogen resistance.</p>\n\t\t\t\t\t\t<p>(B) <i>sek-1(km4)</i> suppresses <i>daf-2(e1370)</i>\n\t\t\t\t\t\t\tenhanced pathogen resistance.</p>\n\t\t\t\t\t\t<p>Slow killing assays were performed with P. aeruginosa strain\n\t\t\t\t\t\t\tPA14 under standard conditions, and each graph shows the average of\n\t\t\t\t\t\t\tthree plates for each strain, with each plate containing 20–30\n\t\t\t\t\t\t\tworms. Results are representative of 3 independent assays. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020183#pgen-0020183-st001\" target=\"_blank\">Table\n\t\t\t\t\t\t\tS1</a> for more assays and statistical analysis.</p></div>", "links"=>[], "tags"=>["pmk-1", "p38", "mapk", "pathway", "pathogen"], "article_id"=>625690, "categories"=>["Genetics", "Immunology", "Infectious Diseases"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0020183.g001", "stats"=>{"downloads"=>4, "page_views"=>102, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_PMK_1_p38_MAPK_Pathway_Is_Required_for_daf_2__Enhanced_Pathogen_Resistance_/625690", "title"=>"The PMK-1 p38 MAPK Pathway Is Required for <i>daf-2</i>\n\t\t\t\t\t\t\tEnhanced Pathogen Resistance", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:05:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/955495"], "description"=>"<div><p>(A) Intensity plot of genes upregulated by PMK-1 in\n\t\t\t\t\t\t\t<i>daf-2(e1368)</i> mutant. Plot represents signal intensity\n\t\t\t\t\t\t\tof all 22,500 sequences on Affymetrix C. elegans GeneChip.\n\t\t\t\t\t\t\tThe <i>x</i>-axis shows expression level in\n\t\t\t\t\t\t\t\t<i>daf-2(e1368);pmk-1(km25)</i> animals and the\n\t\t\t\t\t\t\t<i>y</i>-axis shows expression level in\n\t\t\t\t\t\t\t<i>daf-2(e1368)</i> animals. Sequences colored red are\n\t\t\t\t\t\t\tconsidered upregulated by wild-type PMK-1 and sequences colored green\n\t\t\t\t\t\t\tare considered downregulated by wild-type PMK-1 (using Resolver;\n\t\t\t\t\t\t\t\t<i>p</i> <0.01). Diagonal lines delineate a 2-fold\n\t\t\t\t\t\t\tchange. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020183#pgen-0020183-st002\" target=\"_blank\">Table S2</a> for a complete list of\n\t\t\t\t\t\t\tgenes differentially expressed between <i>daf-2</i> and\n\t\t\t\t\t\t\t\t<i>daf-2;pmk-1</i>.</p>\n\t\t\t\t\t\t<p>(B) Pie chart of gene classes upregulated by PMK-1. The top 36 genes\n\t\t\t\t\t\t\tinduced are represented.</p>\n\t\t\t\t\t\t<p>(C and D) qRT-PCR comparing expression in <i>daf-2(e1368)</i>\n\t\t\t\t\t\t\tversus <i>daf-2(e1368);pmk-1(km25),</i> and\n\t\t\t\t\t\t\t\t<i>daf-2(e1368)</i> versus\n\t\t\t\t\t\t\t\t<i>daf-2(e1368);daf-16(mgDf47).</i> Results are the\n\t\t\t\t\t\t\taverage of two biological replicates, each replicate measured in\n\t\t\t\t\t\t\tduplicate and normalized to a control gene. Error bars are SEM. (C)\n\t\t\t\t\t\t\tshows genes upregulated by PMK-1 and (D) shows genes upregulated by\n\t\t\t\t\t\t\tDAF-16.</p></div>", "links"=>[], "tags"=>["daf-16", "upregulate"], "article_id"=>625777, "categories"=>["Genetics", "Immunology", "Infectious Diseases"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0020183.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PMK_1_and_DAF_16_Upregulate_Distinct_Genes_/625777", "title"=>"PMK-1 and DAF-16 Upregulate Distinct Genes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:06:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/955721"], "description"=>"<div><p>(A) <i>pmk-1(km25)</i> partially suppresses enhanced longevity\n\t\t\t\t\t\t\tof <i>daf-2(e1368)</i>.</p>\n\t\t\t\t\t\t<p>(B) <i>sek-1(km4)</i> partially suppresses enhanced longevity\n\t\t\t\t\t\t\tof <i>daf-2(e1370)</i>.</p>\n\t\t\t\t\t\t<p>See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020183#pgen-0020183-st007\" target=\"_blank\">Table S7</a> for quantitative data.</p></div>", "links"=>[], "tags"=>["pmk-1", "p38", "mapk", "pathway"], "article_id"=>626000, "categories"=>["Genetics", "Immunology", "Infectious Diseases"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0020183.g005", "stats"=>{"downloads"=>3, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_PMK_1_p38_MAPK_Pathway_Is_Partially_Required_for_Increased_Longevity_of_daf_2_/626000", "title"=>"The PMK-1 p38 MAPK Pathway Is Partially Required for Increased\n\t\t\t\t\t\t\tLongevity of <i>daf-2</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:07:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/955654"], "description"=>"<div><p>(A) Venn diagram of overlap between genes regulated by PMK-1 and\n\t\t\t\t\t\t\t\t<i>P. aeruginosa.</i></p>\n\t\t\t\t\t\t<p>(B) (C) qRT-PCR analysis of PA14-induced gene expression in wild-type\n\t\t\t\t\t\t\tanimals and in <i>pmk-1</i> mutants. Results are the average\n\t\t\t\t\t\t\tof two biological replicates, each replicate measured in duplicate and\n\t\t\t\t\t\t\tnormalized to a control gene. Error bars are SEM.</p>\n\t\t\t\t\t\t<p>(D) Diagram of different gene classes regulated by PMK-1 and/or\n\t\t\t\t\t\t\t\t<i>P. aeruginosa.</i> PMK-1 is required for basal and\n\t\t\t\t\t\t\tinducible regulations of class A genes. PMK-1 is required for basal, but\n\t\t\t\t\t\t\tnot inducible expression of class B genes. PMK-1 is required for\n\t\t\t\t\t\t\tinducible but not basal expression of class C genes. PMK-1 is required\n\t\t\t\t\t\t\tfor neither basal nor inducible expression of class D genes. PMK-1\n\t\t\t\t\t\t\tregulates basal expression of class E genes, but these genes are not\n\t\t\t\t\t\t\tinduced by <i>P. aeruginosa.</i></p></div>", "links"=>[], "tags"=>["regulates", "basal", "inducible"], "article_id"=>625934, "categories"=>["Genetics", "Immunology", "Infectious Diseases"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0020183.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PMK_1_Regulates_Basal_and_Inducible_Expression_of_P__aeruginosa_8211_Induced_Genes_/625934", "title"=>"PMK-1 Regulates Basal and Inducible Expression of P.\n\t\t\t\t\t\t\taeruginosa–Induced Genes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:07:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/955795"], "description"=>"<p>We propose that the PMK-1 p38 MAPK pathway plays an active role in\n\t\t\t\t\t\t\tresponse to bacterial pathogens. PMK-1 controls basal levels of pathogen\n\t\t\t\t\t\t\tresponse genes on E.\n\t\t\t\t\t\t\tcoli and also mediates induction of these genes upon\n\t\t\t\t\t\t\tinfection. In contrast, DAF-16 controls a separate group of immune genes\n\t\t\t\t\t\t\tand does not mediate the infection response, but does turn down\n\t\t\t\t\t\t\texpression of some pathogen-induced genes. Certain pathogen response\n\t\t\t\t\t\t\tgenes are induced independently of PMK-1 or DAF-16, indicating the\n\t\t\t\t\t\t\texistence of a third pathway. PMK-1 is required for the enhanced\n\t\t\t\t\t\t\tpathogen resistance of <i>daf-2</i> mutants because it is the\n\t\t\t\t\t\t\tpredominant pathway contributing to immunity. Finally, we suggest that\n\t\t\t\t\t\t\tPMK-1 contributes to enhanced longevity of <i>daf-2</i>\n\t\t\t\t\t\t\tmutants because intact immune function promotes longevity.</p>", "links"=>[], "tags"=>["pmk-1", "p38", "insulin-signaling", "pathway"], "article_id"=>626073, "categories"=>["Genetics", "Immunology", "Infectious Diseases"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0020183.g006", "stats"=>{"downloads"=>7, "page_views"=>486, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Model_for_Regulation_of_Immunity_Longevity_by_the_PMK_1_p38_MAPK_Pathway_and_the_DAF_2_DAF_16_Insulin_Signaling_Pathway_in__C__elegans_/626073", "title"=>"A Model for Regulation of Immunity/Longevity by the PMK-1 p38 MAPK\n\t\t\t\t\t\t\tPathway and the DAF-2–DAF-16 Insulin-Signaling Pathway in\n\t\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\telegans", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:08:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/470384", "https://ndownloader.figshare.com/files/470433", "https://ndownloader.figshare.com/files/470475", "https://ndownloader.figshare.com/files/470522", "https://ndownloader.figshare.com/files/470544", "https://ndownloader.figshare.com/files/470557", "https://ndownloader.figshare.com/files/470576", "https://ndownloader.figshare.com/files/470592", "https://ndownloader.figshare.com/files/470617", "https://ndownloader.figshare.com/files/470638"], "description"=>"<div><p>The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2–DAF-16 insulin signaling pathway control Caenorhabditis elegans intestinal innate immunity. <em>pmk-1</em> loss-of-function mutants have enhanced sensitivity to pathogens, while <em>daf-2</em> loss-of-function mutants have enhanced resistance to pathogens that requires upregulation of the DAF-16 transcription factor. We used genetic analysis to show that the pathogen resistance of <em>daf-2</em> mutants also requires PMK-1. However, genome-wide microarray analysis indicated that there was essentially no overlap between genes positively regulated by PMK-1 and DAF-16, suggesting that they form parallel pathways to promote immunity. We found that PMK-1 controls expression of candidate secreted antimicrobials, including C-type lectins, ShK toxins, and CUB-like genes. Microarray analysis demonstrated that 25% of PMK-1 positively regulated genes are induced by Pseudomonas aeruginosa infection. Using quantitative PCR, we showed that PMK-1 regulates both basal and infection-induced expression of pathogen response genes, while DAF-16 does not. Finally, we used genetic analysis to show that PMK-1 contributes to the enhanced longevity of <em>daf-2</em> mutants. We propose that the PMK-1 pathway is a specific, indispensable immunity pathway that mediates expression of secreted immune response genes, while the DAF-2–DAF-16 pathway appears to regulate immunity as part of a more general stress response. The contribution of the PMK-1 pathway to the enhanced lifespan of <em>daf-2</em> mutants suggests that innate immunity is an important determinant of longevity.</p> </div>", "links"=>[], "tags"=>["p38", "mapk", "regulates", "genes", "longevity"], "article_id"=>152741, "categories"=>["Genetics", "Cancer", "Immunology"], "users"=>["Emily R Troemel", "Stephanie W Chu", "Valerie Reinke", "Siu Sylvia Lee", "Frederick M Ausubel", "Dennis H Kim"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0020183.sg001", "https://dx.doi.org/10.1371/journal.pgen.0020183.sg002", "https://dx.doi.org/10.1371/journal.pgen.0020183.sg003", "https://dx.doi.org/10.1371/journal.pgen.0020183.st001", "https://dx.doi.org/10.1371/journal.pgen.0020183.st002", "https://dx.doi.org/10.1371/journal.pgen.0020183.st003", "https://dx.doi.org/10.1371/journal.pgen.0020183.st004", "https://dx.doi.org/10.1371/journal.pgen.0020183.st005", "https://dx.doi.org/10.1371/journal.pgen.0020183.st006", "https://dx.doi.org/10.1371/journal.pgen.0020183.st007"], "stats"=>{"downloads"=>45, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/p38_MAPK_Regulates_Expression_of_Immune_Response_Genes_and_Contributes_to_Longevity_in_C_elegans_/152741", "title"=>"p38 MAPK Regulates Expression of Immune Response Genes and\n\t\t\t\t\tContributes to Longevity in C.\n\t\t\t\t\t\telegans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2006-11-10 00:45:41"}

PMC Usage Stats | Further Information

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Relative Metric

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