IL-6, but not IFN-γ, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing
STAT1 and STAT3 are the main mediators of the signaling of interferons (IFNs) and of gp130 cytokines, respectively. Neoplastic T lymphocytes frequently become resistant to the IFN-γ/STAT1 apoptotic pathway, often because of the downregulation of the IFN-γR2 receptor chain. Many studies suggest that...
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| creator | Regis, G Icardi, L Conti, L Chiarle, R Piva, R Giovarelli, M Poli, V Novelli, F |
| description | STAT1 and STAT3 are the main mediators of the signaling of interferons (IFNs) and of gp130 cytokines, respectively. Neoplastic T lymphocytes frequently become resistant to the IFN-γ/STAT1 apoptotic pathway, often because of the downregulation of the IFN-γR2 receptor chain. Many studies suggest that cross-regulation between different STATs, in particular between STAT1 and STAT3, may profoundly affect cytokine/growth factor signaling. Here, the function of STAT3 in the negative regulation of STAT1 apoptotic pathway was investigated by RNA interference-mediated STAT3 silencing in human malignant T lymphocytes. In STAT3-depleted cells, interleukin (IL)-6 acquired the capacity to induce apoptosis, correlating with prolonged STAT1 activation and the induction of major histocompatibility complex (MHC) class I expression. In contrast, in the absence of STAT3, IFN-γ could slightly enhance apoptosis but its ability to induce MHC class I expression was unchanged. Accordingly, IL-6, but not IFN-γ, could significantly impair the
in vivo
growth of STAT3-depleted human neoplastic T lymphocytes transplanted into severe combined immunodeficient mice. Therefore, treatment with IL-6 and simultaneous STAT3 silencing may represent a potential therapeutic approach to control the expansion of IFN-γ-unresponsive neoplastic T cells. |
| doi_str_mv | 10.1038/leu.2009.139 |
| format | Article |
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growth of STAT3-depleted human neoplastic T lymphocytes transplanted into severe combined immunodeficient mice. Therefore, treatment with IL-6 and simultaneous STAT3 silencing may represent a potential therapeutic approach to control the expansion of IFN-γ-unresponsive neoplastic T cells.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2009.139</identifier><identifier>PMID: 19626047</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Biological and medical sciences ; Cancer ; Cancer Research ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cellular signal transduction ; Critical Care Medicine ; Cytokines ; Depletion ; Female ; Genes, MHC Class I - physiology ; Genetic aspects ; Glycoprotein gp130 ; Growth factors ; Health aspects ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Immunodeficiency ; Intensive ; Interferon gamma ; Interferon-gamma - metabolism ; Interferon-gamma - pharmacology ; Interleukin 6 ; Interleukin-6 - metabolism ; Interleukin-6 - pharmacology ; Internal Medicine ; Lymphocytes ; Lymphocytes T ; Lymphoma, T-Cell - metabolism ; Lymphoma, T-Cell - pathology ; Major histocompatibility complex ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Oncology ; original-article ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; RNA, Small Interfering ; RNA-mediated interference ; Signal transduction ; Signal Transduction - physiology ; Signaling ; Stat1 protein ; STAT1 Transcription Factor - metabolism ; Stat3 protein ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; T-Lymphocytes - cytology ; T-Lymphocytes - metabolism ; γ-Interferon</subject><ispartof>Leukemia, 2009-11, Vol.23 (11), p.2102-2108</ispartof><rights>Macmillan Publishers Limited 2009</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2009.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-d57a502500c5711ed9b2afcc7b93de7a97469c18ec3b5c19c22483a8412fdb513</citedby><cites>FETCH-LOGICAL-c522t-d57a502500c5711ed9b2afcc7b93de7a97469c18ec3b5c19c22483a8412fdb513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22149419$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19626047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Regis, G</creatorcontrib><creatorcontrib>Icardi, L</creatorcontrib><creatorcontrib>Conti, L</creatorcontrib><creatorcontrib>Chiarle, R</creatorcontrib><creatorcontrib>Piva, R</creatorcontrib><creatorcontrib>Giovarelli, M</creatorcontrib><creatorcontrib>Poli, V</creatorcontrib><creatorcontrib>Novelli, F</creatorcontrib><title>IL-6, but not IFN-γ, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>STAT1 and STAT3 are the main mediators of the signaling of interferons (IFNs) and of gp130 cytokines, respectively. Neoplastic T lymphocytes frequently become resistant to the IFN-γ/STAT1 apoptotic pathway, often because of the downregulation of the IFN-γR2 receptor chain. Many studies suggest that cross-regulation between different STATs, in particular between STAT1 and STAT3, may profoundly affect cytokine/growth factor signaling. Here, the function of STAT3 in the negative regulation of STAT1 apoptotic pathway was investigated by RNA interference-mediated STAT3 silencing in human malignant T lymphocytes. In STAT3-depleted cells, interleukin (IL)-6 acquired the capacity to induce apoptosis, correlating with prolonged STAT1 activation and the induction of major histocompatibility complex (MHC) class I expression. In contrast, in the absence of STAT3, IFN-γ could slightly enhance apoptosis but its ability to induce MHC class I expression was unchanged. Accordingly, IL-6, but not IFN-γ, could significantly impair the
in vivo
growth of STAT3-depleted human neoplastic T lymphocytes transplanted into severe combined immunodeficient mice. Therefore, treatment with IL-6 and simultaneous STAT3 silencing may represent a potential therapeutic approach to control the expansion of IFN-γ-unresponsive neoplastic T cells.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cellular signal transduction</subject><subject>Critical Care Medicine</subject><subject>Cytokines</subject><subject>Depletion</subject><subject>Female</subject><subject>Genes, MHC Class I - physiology</subject><subject>Genetic aspects</subject><subject>Glycoprotein gp130</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunodeficiency</subject><subject>Intensive</subject><subject>Interferon gamma</subject><subject>Interferon-gamma - 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physiology</subject><subject>Signaling</subject><subject>Stat1 protein</subject><subject>STAT1 Transcription Factor - metabolism</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - metabolism</subject><subject>γ-Interferon</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkk1v0zAYxy0EYmVw44wsIeDSFNuxk_hYTRtUquBAOVuO46SeHLvYzhCfi--xz4SjVpShyQc_0vN73v8AvMZohVHZfLR6WhGE-AqX_AlYYFpXBWMMPwUL1DR1UXFCL8CLGG8Rmp3Vc3CBeUUqROsFCJttUS1hOyXofIKbmy_F_e8lTMEMgw4RyoM_JB9NtlwHjdub1qSYDXhn7jwcgv-Z9tD3cD-N0sFRWjM46RLcQaWtjdA7-G233pUwGqudMm54CZ710kb96vRfgu8317urz8X266fN1XpbKEZIKjpWS4YIQ0ixGmPd8ZbIXqm65WWna8lrWnGFG63KlinMFSG0KWVDMem7luHyEnw45j0E_2PSMYnRxLkp6bSfoqhLiktGKcnk2__IWz8Fl5sTpKK5OqMNO1ODtFoY1_sUpJpzijXBhDUVoShTq0eo_Do9GuWd7vMeHga8_ydgr6VN--jtlIx38SG4PIIq-BiD7sUhmFGGXwIjMUtBZCmIWQoiSyHjb05DTe2ouzN8un0G3p0AGZW0fZD5PPEvRwimnOI5UXHkYna5rIrzdh4t_AdxFscC</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Regis, G</creator><creator>Icardi, L</creator><creator>Conti, L</creator><creator>Chiarle, R</creator><creator>Piva, R</creator><creator>Giovarelli, M</creator><creator>Poli, V</creator><creator>Novelli, F</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20091101</creationdate><title>IL-6, but not IFN-γ, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing</title><author>Regis, G ; Icardi, L ; Conti, L ; Chiarle, R ; Piva, R ; Giovarelli, M ; Poli, V ; Novelli, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-d57a502500c5711ed9b2afcc7b93de7a97469c18ec3b5c19c22483a8412fdb513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cellular signal transduction</topic><topic>Critical Care Medicine</topic><topic>Cytokines</topic><topic>Depletion</topic><topic>Female</topic><topic>Genes, MHC Class I - physiology</topic><topic>Genetic aspects</topic><topic>Glycoprotein gp130</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunodeficiency</topic><topic>Intensive</topic><topic>Interferon gamma</topic><topic>Interferon-gamma - metabolism</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - metabolism</topic><topic>Interleukin-6 - pharmacology</topic><topic>Internal Medicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphoma, T-Cell - 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Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Regis, G</au><au>Icardi, L</au><au>Conti, L</au><au>Chiarle, R</au><au>Piva, R</au><au>Giovarelli, M</au><au>Poli, V</au><au>Novelli, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-6, but not IFN-γ, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>23</volume><issue>11</issue><spage>2102</spage><epage>2108</epage><pages>2102-2108</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>STAT1 and STAT3 are the main mediators of the signaling of interferons (IFNs) and of gp130 cytokines, respectively. Neoplastic T lymphocytes frequently become resistant to the IFN-γ/STAT1 apoptotic pathway, often because of the downregulation of the IFN-γR2 receptor chain. Many studies suggest that cross-regulation between different STATs, in particular between STAT1 and STAT3, may profoundly affect cytokine/growth factor signaling. Here, the function of STAT3 in the negative regulation of STAT1 apoptotic pathway was investigated by RNA interference-mediated STAT3 silencing in human malignant T lymphocytes. In STAT3-depleted cells, interleukin (IL)-6 acquired the capacity to induce apoptosis, correlating with prolonged STAT1 activation and the induction of major histocompatibility complex (MHC) class I expression. In contrast, in the absence of STAT3, IFN-γ could slightly enhance apoptosis but its ability to induce MHC class I expression was unchanged. Accordingly, IL-6, but not IFN-γ, could significantly impair the
in vivo
growth of STAT3-depleted human neoplastic T lymphocytes transplanted into severe combined immunodeficient mice. Therefore, treatment with IL-6 and simultaneous STAT3 silencing may represent a potential therapeutic approach to control the expansion of IFN-γ-unresponsive neoplastic T cells.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19626047</pmid><doi>10.1038/leu.2009.139</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Apoptosis Apoptosis - drug effects Apoptosis - physiology Biological and medical sciences Cancer Cancer Research Cell Line, Tumor Cell Proliferation - drug effects Cellular signal transduction Critical Care Medicine Cytokines Depletion Female Genes, MHC Class I - physiology Genetic aspects Glycoprotein gp130 Growth factors Health aspects Hematologic and hematopoietic diseases Hematology Humans Immunodeficiency Intensive Interferon gamma Interferon-gamma - metabolism Interferon-gamma - pharmacology Interleukin 6 Interleukin-6 - metabolism Interleukin-6 - pharmacology Internal Medicine Lymphocytes Lymphocytes T Lymphoma, T-Cell - metabolism Lymphoma, T-Cell - pathology Major histocompatibility complex Medical sciences Medicine Medicine & Public Health Mice Mice, SCID Neoplasm Transplantation Oncology original-article Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology RNA, Small Interfering RNA-mediated interference Signal transduction Signal Transduction - physiology Signaling Stat1 protein STAT1 Transcription Factor - metabolism Stat3 protein STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism T-Lymphocytes - cytology T-Lymphocytes - metabolism γ-Interferon |
| title | IL-6, but not IFN-γ, triggers apoptosis and inhibits in vivo growth of human malignant T cells on STAT3 silencing |
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