Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells
Activation of antigen‐presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG‐DNA) initiates immune responses. We have analyzed the mitogen‐activated protein kinase (MAPK) pathways triggered by CpG‐DNA and their significance for cytokine...
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| Veröffentlicht in: | The EMBO journal 1999-12, Vol.18 (24), p.6973-6982 |
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| creator | Häcker, Hans Mischak, Harald Häcker, Georg Eser, Sema Prenzel, Norbert Ullrich, Axel Wagner, Hermann |
| description | Activation of antigen‐presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG‐DNA) initiates immune responses. We have analyzed the mitogen‐activated protein kinase (MAPK) pathways triggered by CpG‐DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG‐DNA induced extracellular signal‐regulated kinase (ERK) activity in macrophages in a classic MEK‐dependent way. This pathway up‐regulated tumor necrosis factor production but down‐regulated interleukin (IL)‐12 production. However, in DCs, which produce large amounts of IL‐12, CpG‐DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG‐DNA‐induced IL‐12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions. |
| doi_str_mv | 10.1093/emboj/18.24.6973 |
| format | Article |
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We have analyzed the mitogen‐activated protein kinase (MAPK) pathways triggered by CpG‐DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG‐DNA induced extracellular signal‐regulated kinase (ERK) activity in macrophages in a classic MEK‐dependent way. This pathway up‐regulated tumor necrosis factor production but down‐regulated interleukin (IL)‐12 production. However, in DCs, which produce large amounts of IL‐12, CpG‐DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG‐DNA‐induced IL‐12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/18.24.6973</identifier><identifier>PMID: 10601019</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Antigen-Presenting Cells - drug effects ; Antigen-Presenting Cells - immunology ; Antigen-Presenting Cells - physiology ; Bone Marrow Cells - cytology ; Bone Marrow Cells - immunology ; Cell Line ; Cells, Cultured ; CpG-DNA ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - physiology ; Deoxyribonucleic acid ; Dinucleoside Phosphates ; DNA ; ERK kinase ; ERK protein ; Gene Expression Regulation - immunology ; IL-12 ; innate immunity ; Interleukin-12 - biosynthesis ; Interleukin-12 - genetics ; lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Luciferases - genetics ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - physiology ; MAP kinase ; MEK protein ; Mice ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinases - metabolism ; Oligodeoxyribonucleotides - pharmacology ; Recombinant Proteins - biosynthesis ; Thionucleotides ; TNF ; Transfection ; Tumor Necrosis Factor-alpha - genetics</subject><ispartof>The EMBO journal, 1999-12, Vol.18 (24), p.6973-6982</ispartof><rights>European Molecular Biology Organization 1999</rights><rights>Copyright © 1999 European Molecular Biology Organization</rights><rights>Copyright Oxford University Press(England) Dec 15, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6468-96b9c1cd6641e1ae476cfb2c20357d85d0e5bc9b9bc3d902032713db3d229f6d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171760/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171760/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10601019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Häcker, Hans</creatorcontrib><creatorcontrib>Mischak, Harald</creatorcontrib><creatorcontrib>Häcker, Georg</creatorcontrib><creatorcontrib>Eser, Sema</creatorcontrib><creatorcontrib>Prenzel, Norbert</creatorcontrib><creatorcontrib>Ullrich, Axel</creatorcontrib><creatorcontrib>Wagner, Hermann</creatorcontrib><title>Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Activation of antigen‐presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG‐DNA) initiates immune responses. We have analyzed the mitogen‐activated protein kinase (MAPK) pathways triggered by CpG‐DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG‐DNA induced extracellular signal‐regulated kinase (ERK) activity in macrophages in a classic MEK‐dependent way. This pathway up‐regulated tumor necrosis factor production but down‐regulated interleukin (IL)‐12 production. However, in DCs, which produce large amounts of IL‐12, CpG‐DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG‐DNA‐induced IL‐12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.</description><subject>Animals</subject><subject>Antigen-Presenting Cells - drug effects</subject><subject>Antigen-Presenting Cells - immunology</subject><subject>Antigen-Presenting Cells - physiology</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - immunology</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>CpG-DNA</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - physiology</subject><subject>Deoxyribonucleic acid</subject><subject>Dinucleoside Phosphates</subject><subject>DNA</subject><subject>ERK kinase</subject><subject>ERK protein</subject><subject>Gene Expression Regulation - immunology</subject><subject>IL-12</subject><subject>innate immunity</subject><subject>Interleukin-12 - biosynthesis</subject><subject>Interleukin-12 - genetics</subject><subject>lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Luciferases - genetics</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - physiology</subject><subject>MAP kinase</subject><subject>MEK protein</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Oligodeoxyribonucleotides - pharmacology</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Thionucleotides</subject><subject>TNF</subject><subject>Transfection</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEoqWwZ4UsFuwy9XUSO94gtUMZGJUiVfwsrcS5GTxN7GBnCvMMvDQeMqoGJNSVLfs7x-daJ0meA50Bldkp9rVbn0I5Y_mMS5E9SI4h5zRlVBQPk2PKOKQ5lPIoeRLCmlJalAIeJ0dAOQUK8jj5NceuI-N2wDQMqE1rNKn0aG6r0ThLXEt6M7oV2nR_ig0ZvBvRWHJjbBUwkHpL5sMifXN1RrSzo3ddIMaO6DvcRCYFRjx2GFnSeteTyo5m5zh4DBj3dkV0TBGeJo_aqgv4bL-eJJ_fXnyav0svPy7ez88uU81zXqaS11KDbjjPAaHCXHDd1kwzmhWiKYuGYlFrWctaZ42k8ZgJyJo6axiTLW-yk-T15Dts6h4bHTP4qlODN33lt8pVRv19Y803tXK3CkCA4DQavNobePd9g2FUvQm7ESqLbhMUlxmnJch7QRC5YIJnEXz5D7h2G2_jLyiQBSsKznmE6ARp70Lw2N5FBqp2fVB_-qCgVCxXuz5EyYvDUQ8EUwEiICfgh-lwe6-huvhwvhSFZFSWUQuTNkSZXaE_CP3_QOmkMWHEn3fvVf5GcZGJQn29WqjrL0sul9dzlWW_AQcM5i4</recordid><startdate>19991215</startdate><enddate>19991215</enddate><creator>Häcker, Hans</creator><creator>Mischak, Harald</creator><creator>Häcker, Georg</creator><creator>Eser, Sema</creator><creator>Prenzel, Norbert</creator><creator>Ullrich, Axel</creator><creator>Wagner, Hermann</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19991215</creationdate><title>Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells</title><author>Häcker, Hans ; Mischak, Harald ; Häcker, Georg ; Eser, Sema ; Prenzel, Norbert ; Ullrich, Axel ; Wagner, Hermann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6468-96b9c1cd6641e1ae476cfb2c20357d85d0e5bc9b9bc3d902032713db3d229f6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Antigen-Presenting Cells - drug effects</topic><topic>Antigen-Presenting Cells - immunology</topic><topic>Antigen-Presenting Cells - physiology</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone Marrow Cells - immunology</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>CpG-DNA</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - physiology</topic><topic>Deoxyribonucleic acid</topic><topic>Dinucleoside Phosphates</topic><topic>DNA</topic><topic>ERK kinase</topic><topic>ERK protein</topic><topic>Gene Expression Regulation - immunology</topic><topic>IL-12</topic><topic>innate immunity</topic><topic>Interleukin-12 - biosynthesis</topic><topic>Interleukin-12 - genetics</topic><topic>lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Luciferases - genetics</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - physiology</topic><topic>MAP kinase</topic><topic>MEK protein</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Oligodeoxyribonucleotides - pharmacology</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Thionucleotides</topic><topic>TNF</topic><topic>Transfection</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Häcker, Hans</creatorcontrib><creatorcontrib>Mischak, Harald</creatorcontrib><creatorcontrib>Häcker, Georg</creatorcontrib><creatorcontrib>Eser, Sema</creatorcontrib><creatorcontrib>Prenzel, Norbert</creatorcontrib><creatorcontrib>Ullrich, Axel</creatorcontrib><creatorcontrib>Wagner, Hermann</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Häcker, Hans</au><au>Mischak, Harald</au><au>Häcker, Georg</au><au>Eser, Sema</au><au>Prenzel, Norbert</au><au>Ullrich, Axel</au><au>Wagner, Hermann</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>1999-12-15</date><risdate>1999</risdate><volume>18</volume><issue>24</issue><spage>6973</spage><epage>6982</epage><pages>6973-6982</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Activation of antigen‐presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG‐DNA) initiates immune responses. We have analyzed the mitogen‐activated protein kinase (MAPK) pathways triggered by CpG‐DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG‐DNA induced extracellular signal‐regulated kinase (ERK) activity in macrophages in a classic MEK‐dependent way. This pathway up‐regulated tumor necrosis factor production but down‐regulated interleukin (IL)‐12 production. However, in DCs, which produce large amounts of IL‐12, CpG‐DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG‐DNA‐induced IL‐12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>10601019</pmid><doi>10.1093/emboj/18.24.6973</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0261-4189 1460-2075 1460-2075 |
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| subjects | Animals Antigen-Presenting Cells - drug effects Antigen-Presenting Cells - immunology Antigen-Presenting Cells - physiology Bone Marrow Cells - cytology Bone Marrow Cells - immunology Cell Line Cells, Cultured CpG-DNA Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - physiology Deoxyribonucleic acid Dinucleoside Phosphates DNA ERK kinase ERK protein Gene Expression Regulation - immunology IL-12 innate immunity Interleukin-12 - biosynthesis Interleukin-12 - genetics lipopolysaccharides Lipopolysaccharides - pharmacology Luciferases - genetics Macrophages - drug effects Macrophages - immunology Macrophages - physiology MAP kinase MEK protein Mice Mice, Inbred C57BL Mitogen-Activated Protein Kinases - metabolism Oligodeoxyribonucleotides - pharmacology Recombinant Proteins - biosynthesis Thionucleotides TNF Transfection Tumor Necrosis Factor-alpha - genetics |
| title | Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells |
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