Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity
Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural kill...
Gespeichert in:
| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1999-05, Vol.284 (5416), p.951-955 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 955 |
|---|---|
| container_issue | 5416 |
| container_start_page | 951 |
| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 284 |
| creator | Diefenbach, Andreas Schindler, Heike Röllinghoff, Martin Yokoyama, Wayne M. Bogdan, Christian |
| description | Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-γ (IFN-γ) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity. |
| doi_str_mv | 10.1126/science.284.5416.951 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_743738032</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A54711368</galeid><jstor_id>2899203</jstor_id><sourcerecordid>A54711368</sourcerecordid><originalsourceid>FETCH-LOGICAL-c717t-b3567921c14df5caef3c772489382110542f777642ec477c51d08d9f553759593</originalsourceid><addsrcrecordid>eNqN0--L0zAYB_Aiirc7_Q8OKSLqi-vMj6ZJXp5DZ2HcwJ2-Dbnsac1o013SgvvvL7sNdTJ05EUg-STkSb5JkkuMxhiT4kMwFpyBMRH5mOW4GEuGnyQjjCTLJEH0aTJCiBaZQJydJechrBCKc5I-T84wolFwOkrKr3A_WA8tuD6tOp_ebtaQkvRmni42rv-hAzwOl7MMk3Rha6cb6-rUurR0TveQlm07ONtvXiTPKt0EeLnvL5Jvnz_dTr5ks_m0nFzPMsMx77M7ygouCTY4X1bMaKio4ZzkQlJBMEYsJxXnvMgJmJxzw_ASiaWsGKOcbY9_kbzb7bv23f0AoVetDQaaRjvohqB4HgsTscAo3_5TFpIXSOL_Q8wJlkKwCF__BVfd4OOVBEVwLCzC7W5XO1TrBpR1Vdd7bWpw4HXTOahsHL5mOceYFiLy7AiPbQmtNcf8-wMfSQ8_-1oPIahycXMynX8_mX6cnkrFdHZAr45R0zUN1KBiLibzA57vuPFdCB4qtfa21X6jMFLb0Kt96FUMvdqGXsXQx2Wv9q8y3LWw_GPRLuURvNkDHYxuKq-dseG3i2lhjzG43LFV6Dv_a5oIuf1P9AG0QgtH</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>213561722</pqid></control><display><type>article</type><title>Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity</title><source>MEDLINE</source><source>Science Magazine</source><source>JSTOR Archive Collection A-Z Listing</source><creator>Diefenbach, Andreas ; Schindler, Heike ; Röllinghoff, Martin ; Yokoyama, Wayne M. ; Bogdan, Christian</creator><creatorcontrib>Diefenbach, Andreas ; Schindler, Heike ; Röllinghoff, Martin ; Yokoyama, Wayne M. ; Bogdan, Christian</creatorcontrib><description>Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-γ (IFN-γ) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.284.5416.951</identifier><identifier>PMID: 10320373</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Analysis of the immune response. Humoral and cellular immunity ; Animals ; Biological and medical sciences ; Cell lines ; Cells, Cultured ; Cellular biology ; Cultured cells ; Cyclic GMP - metabolism ; Cytotoxicity, Immunologic ; DNA-Binding Proteins - metabolism ; Enzyme Activation ; Enzyme Inhibitors - pharmacology ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Immune system ; Immunity, Innate ; Immunobiology ; Infections ; Innate immunity ; Interferon-gamma - biosynthesis ; Interferon-gamma - genetics ; Interferons - pharmacology ; Interleukin-12 ; Interleukin-12 - pharmacology ; Interleukin-12 - physiology ; Janus Kinase 2 ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Leishmania ; Leishmania major ; Leishmaniasis, Cutaneous - immunology ; Leishmaniasis, Cutaneous - metabolism ; Life cycle. Host-agent relationship. Pathogenesis ; Lymphokines, interleukins ( function, expression) ; Lysine - analogs & derivatives ; Lysine - pharmacology ; Messenger RNA ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microbiology ; Natural killer cells ; Nitric Oxide - metabolism ; Nitric Oxide Synthase - antagonists & inhibitors ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Parasites ; Pathogenic microorganisms ; Phosphorylation ; Protein-Tyrosine Kinases - metabolism ; Proteins - metabolism ; Proto-Oncogene Proteins ; Protozoa ; Regulatory factors and their cellular receptors ; Signal Transduction ; Sodium ; STAT4 Transcription Factor ; T lymphocytes ; Trans-Activators - metabolism ; TYK2 Kinase ; Up-Regulation</subject><ispartof>Science (American Association for the Advancement of Science), 1999-05, Vol.284 (5416), p.951-955</ispartof><rights>Copyright 1999 American Association for the Advancement of Science</rights><rights>1999 INIST-CNRS</rights><rights>COPYRIGHT 1999 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1999 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science May 7, 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c717t-b3567921c14df5caef3c772489382110542f777642ec477c51d08d9f553759593</citedby><cites>FETCH-LOGICAL-c717t-b3567921c14df5caef3c772489382110542f777642ec477c51d08d9f553759593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2899203$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2899203$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1803512$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10320373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Diefenbach, Andreas</creatorcontrib><creatorcontrib>Schindler, Heike</creatorcontrib><creatorcontrib>Röllinghoff, Martin</creatorcontrib><creatorcontrib>Yokoyama, Wayne M.</creatorcontrib><creatorcontrib>Bogdan, Christian</creatorcontrib><title>Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-γ (IFN-γ) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.</description><subject>Analysis of the immune response. Humoral and cellular immunity</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell lines</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Cultured cells</subject><subject>Cyclic GMP - metabolism</subject><subject>Cytotoxicity, Immunologic</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Enzyme Activation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Immune system</subject><subject>Immunity, Innate</subject><subject>Immunobiology</subject><subject>Infections</subject><subject>Innate immunity</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interferon-gamma - genetics</subject><subject>Interferons - pharmacology</subject><subject>Interleukin-12</subject><subject>Interleukin-12 - pharmacology</subject><subject>Interleukin-12 - physiology</subject><subject>Janus Kinase 2</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Leishmania</subject><subject>Leishmania major</subject><subject>Leishmaniasis, Cutaneous - immunology</subject><subject>Leishmaniasis, Cutaneous - metabolism</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Lymphokines, interleukins ( function, expression)</subject><subject>Lysine - analogs & derivatives</subject><subject>Lysine - pharmacology</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology</subject><subject>Natural killer cells</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Parasites</subject><subject>Pathogenic microorganisms</subject><subject>Phosphorylation</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proteins - metabolism</subject><subject>Proto-Oncogene Proteins</subject><subject>Protozoa</subject><subject>Regulatory factors and their cellular receptors</subject><subject>Signal Transduction</subject><subject>Sodium</subject><subject>STAT4 Transcription Factor</subject><subject>T lymphocytes</subject><subject>Trans-Activators - metabolism</subject><subject>TYK2 Kinase</subject><subject>Up-Regulation</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0--L0zAYB_Aiirc7_Q8OKSLqi-vMj6ZJXp5DZ2HcwJ2-Dbnsac1o013SgvvvL7sNdTJ05EUg-STkSb5JkkuMxhiT4kMwFpyBMRH5mOW4GEuGnyQjjCTLJEH0aTJCiBaZQJydJechrBCKc5I-T84wolFwOkrKr3A_WA8tuD6tOp_ebtaQkvRmni42rv-hAzwOl7MMk3Rha6cb6-rUurR0TveQlm07ONtvXiTPKt0EeLnvL5Jvnz_dTr5ks_m0nFzPMsMx77M7ygouCTY4X1bMaKio4ZzkQlJBMEYsJxXnvMgJmJxzw_ASiaWsGKOcbY9_kbzb7bv23f0AoVetDQaaRjvohqB4HgsTscAo3_5TFpIXSOL_Q8wJlkKwCF__BVfd4OOVBEVwLCzC7W5XO1TrBpR1Vdd7bWpw4HXTOahsHL5mOceYFiLy7AiPbQmtNcf8-wMfSQ8_-1oPIahycXMynX8_mX6cnkrFdHZAr45R0zUN1KBiLibzA57vuPFdCB4qtfa21X6jMFLb0Kt96FUMvdqGXsXQx2Wv9q8y3LWw_GPRLuURvNkDHYxuKq-dseG3i2lhjzG43LFV6Dv_a5oIuf1P9AG0QgtH</recordid><startdate>19990507</startdate><enddate>19990507</enddate><creator>Diefenbach, Andreas</creator><creator>Schindler, Heike</creator><creator>Röllinghoff, Martin</creator><creator>Yokoyama, Wayne M.</creator><creator>Bogdan, Christian</creator><general>American Society for the Advancement of Science</general><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>IQODW</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>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>0-V</scope><scope>3V.</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88B</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CJNVE</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9-</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0K</scope><scope>M0P</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEDU</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>7T5</scope><scope>7X8</scope></search><sort><creationdate>19990507</creationdate><title>Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity</title><author>Diefenbach, Andreas ; Schindler, Heike ; Röllinghoff, Martin ; Yokoyama, Wayne M. ; Bogdan, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c717t-b3567921c14df5caef3c772489382110542f777642ec477c51d08d9f553759593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Analysis of the immune response. Humoral and cellular immunity</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell lines</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Cultured cells</topic><topic>Cyclic GMP - metabolism</topic><topic>Cytotoxicity, Immunologic</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Enzyme Activation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Immune system</topic><topic>Immunity, Innate</topic><topic>Immunobiology</topic><topic>Infections</topic><topic>Innate immunity</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interferon-gamma - genetics</topic><topic>Interferons - pharmacology</topic><topic>Interleukin-12</topic><topic>Interleukin-12 - pharmacology</topic><topic>Interleukin-12 - physiology</topic><topic>Janus Kinase 2</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Leishmania</topic><topic>Leishmania major</topic><topic>Leishmaniasis, Cutaneous - immunology</topic><topic>Leishmaniasis, Cutaneous - metabolism</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Lymphokines, interleukins ( function, expression)</topic><topic>Lysine - analogs & derivatives</topic><topic>Lysine - pharmacology</topic><topic>Messenger RNA</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiology</topic><topic>Natural killer cells</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Parasites</topic><topic>Pathogenic microorganisms</topic><topic>Phosphorylation</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proteins - metabolism</topic><topic>Proto-Oncogene Proteins</topic><topic>Protozoa</topic><topic>Regulatory factors and their cellular receptors</topic><topic>Signal Transduction</topic><topic>Sodium</topic><topic>STAT4 Transcription Factor</topic><topic>T lymphocytes</topic><topic>Trans-Activators - metabolism</topic><topic>TYK2 Kinase</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Diefenbach, Andreas</creatorcontrib><creatorcontrib>Schindler, Heike</creatorcontrib><creatorcontrib>Röllinghoff, Martin</creatorcontrib><creatorcontrib>Yokoyama, Wayne M.</creatorcontrib><creatorcontrib>Bogdan, Christian</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>Gale In Context: Biography</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Education Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Education Collection</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Agricultural Science Database</collection><collection>Education Database</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Education</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>Immunology Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Diefenbach, Andreas</au><au>Schindler, Heike</au><au>Röllinghoff, Martin</au><au>Yokoyama, Wayne M.</au><au>Bogdan, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>1999-05-07</date><risdate>1999</risdate><volume>284</volume><issue>5416</issue><spage>951</spage><epage>955</epage><pages>951-955</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-γ (IFN-γ) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-α/β also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>10320373</pmid><doi>10.1126/science.284.5416.951</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1999-05, Vol.284 (5416), p.951-955 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743738032 |
| source | MEDLINE; Science Magazine; JSTOR Archive Collection A-Z Listing |
| subjects | Analysis of the immune response. Humoral and cellular immunity Animals Biological and medical sciences Cell lines Cells, Cultured Cellular biology Cultured cells Cyclic GMP - metabolism Cytotoxicity, Immunologic DNA-Binding Proteins - metabolism Enzyme Activation Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Fundamental immunology Immune system Immunity, Innate Immunobiology Infections Innate immunity Interferon-gamma - biosynthesis Interferon-gamma - genetics Interferons - pharmacology Interleukin-12 Interleukin-12 - pharmacology Interleukin-12 - physiology Janus Kinase 2 Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Leishmania Leishmania major Leishmaniasis, Cutaneous - immunology Leishmaniasis, Cutaneous - metabolism Life cycle. Host-agent relationship. Pathogenesis Lymphokines, interleukins ( function, expression) Lysine - analogs & derivatives Lysine - pharmacology Messenger RNA Mice Mice, Inbred BALB C Mice, Inbred C57BL Microbiology Natural killer cells Nitric Oxide - metabolism Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Parasites Pathogenic microorganisms Phosphorylation Protein-Tyrosine Kinases - metabolism Proteins - metabolism Proto-Oncogene Proteins Protozoa Regulatory factors and their cellular receptors Signal Transduction Sodium STAT4 Transcription Factor T lymphocytes Trans-Activators - metabolism TYK2 Kinase Up-Regulation |
| title | Requirement for Type 2 NO Synthase for IL-12 Signaling in Innate Immunity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T09%3A23%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Requirement%20for%20Type%202%20NO%20Synthase%20for%20IL-12%20Signaling%20in%20Innate%20Immunity&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Diefenbach,%20Andreas&rft.date=1999-05-07&rft.volume=284&rft.issue=5416&rft.spage=951&rft.epage=955&rft.pages=951-955&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.284.5416.951&rft_dat=%3Cgale_proqu%3EA54711368%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=213561722&rft_id=info:pmid/10320373&rft_galeid=A54711368&rft_jstor_id=2899203&rfr_iscdi=true |