Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system
CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis...
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Veröffentlicht in: | Journal of neuroimmunology 2005-05, Vol.162 (1), p.28-42 |
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container_title | Journal of neuroimmunology |
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creator | Wischhusen, Jörg Schneider, Dagmar Mittelbronn, Michel Meyermann, Richard Engelmann, Hartmut Jung, Gundram Wiendl, Heinz Weller, Michael |
description | CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-α-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling. |
doi_str_mv | 10.1016/j.jneuroim.2005.01.005 |
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Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-α-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.</description><identifier>ISSN: 0165-5728</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2005.01.005</identifier><identifier>PMID: 15833357</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Amino Acid Chloromethyl Ketones - pharmacology ; Antibodies - pharmacology ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - physiology ; Bispecific antibodies ; Blotting, Northern - methods ; Blotting, Western - methods ; Caspases - metabolism ; CD40 ; CD40 Antigens - immunology ; CD40 Antigens - pharmacology ; CD40 Antigens - physiology ; CD40 Ligand - pharmacology ; CD40 Ligand - physiology ; Cell Line, Tumor ; Cell Survival - drug effects ; Cell Survival - physiology ; Collagen Type XI - metabolism ; Dose-Response Relationship, Drug ; Drug Interactions ; Fas Ligand Protein ; fas Receptor - immunology ; fas Receptor - metabolism ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - physiology ; Glioma ; Glioma - metabolism ; Glioma - pathology ; Humans ; Immunohistochemistry - methods ; Immunoprecipitation - methods ; Leupeptins - pharmacology ; Membrane Glycoproteins - pharmacology ; Neuroprotective Agents - pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Reverse Transcriptase Polymerase Chain Reaction - methods ; RNA Interference - physiology ; RNA, Messenger - biosynthesis ; Time Factors ; TNF-R1 (p55) ; Transfection - methods ; Tumor Necrosis Factor-alpha - metabolism ; Tumor Necrosis Factor-alpha - pharmacology</subject><ispartof>Journal of neuroimmunology, 2005-05, Vol.162 (1), p.28-42</ispartof><rights>2005 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-fad500ced0d22484df8bc76e1f691cd07e894edcfa91b01c7638cd23343386c03</citedby><cites>FETCH-LOGICAL-c494t-fad500ced0d22484df8bc76e1f691cd07e894edcfa91b01c7638cd23343386c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneuroim.2005.01.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15833357$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wischhusen, Jörg</creatorcontrib><creatorcontrib>Schneider, Dagmar</creatorcontrib><creatorcontrib>Mittelbronn, Michel</creatorcontrib><creatorcontrib>Meyermann, Richard</creatorcontrib><creatorcontrib>Engelmann, Hartmut</creatorcontrib><creatorcontrib>Jung, Gundram</creatorcontrib><creatorcontrib>Wiendl, Heinz</creatorcontrib><creatorcontrib>Weller, Michael</creatorcontrib><title>Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-α-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.</description><subject>Amino Acid Chloromethyl Ketones - pharmacology</subject><subject>Antibodies - pharmacology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Bispecific antibodies</subject><subject>Blotting, Northern - methods</subject><subject>Blotting, Western - methods</subject><subject>Caspases - metabolism</subject><subject>CD40</subject><subject>CD40 Antigens - immunology</subject><subject>CD40 Antigens - pharmacology</subject><subject>CD40 Antigens - physiology</subject><subject>CD40 Ligand - pharmacology</subject><subject>CD40 Ligand - physiology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Collagen Type XI - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Interactions</subject><subject>Fas Ligand Protein</subject><subject>fas Receptor - immunology</subject><subject>fas Receptor - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - physiology</subject><subject>Glioma</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Immunoprecipitation - methods</subject><subject>Leupeptins - pharmacology</subject><subject>Membrane Glycoproteins - pharmacology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Poly (ADP-Ribose) Polymerase-1</subject><subject>Poly(ADP-ribose) Polymerases</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>RNA Interference - physiology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Time Factors</subject><subject>TNF-R1 (p55)</subject><subject>Transfection - methods</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v3CAQxVGVqtkk_QoRp97sDAbbuKdGmz-ttFUuyRmxMM6yss0WcKT99mG1G_WYC0-C38ww7xFyzaBkwJqbbbmdcA7ejWUFUJfAyixfyILJtiqkqNgZWWSwLuq2kufkIsYtAKu56L6Rc1ZLznndLkh_hzptaECDu-RDMaJ1OqGleufzRXSRuolu5lFPdNSDe530lOjr4PyoqcFhiD_pX2_nQSfnJ7re07RBurwTcHM4VjTuY8Lxinzt9RDx-0kvycvD_fPyd7F6evyzvF0VRnQiFb22NYBBC7aqhBS2l2vTNsj6pmPGQouyE2hNrzu2BpafuDS24lxwLhsD_JL8OPbdBf9vxpjU6OLhm3pCP0dVQQtdnbf_DGQtF7k7z2BzBE3wMQbs1S64UYe9YqAOUait-ohCHaJQwFSWXHh9mjCvs6v_y07eZ-DXEcBsyJvDoKJxOOXtXY4jKevdZzPeAXp1ngg</recordid><startdate>20050501</startdate><enddate>20050501</enddate><creator>Wischhusen, Jörg</creator><creator>Schneider, Dagmar</creator><creator>Mittelbronn, Michel</creator><creator>Meyermann, Richard</creator><creator>Engelmann, Hartmut</creator><creator>Jung, Gundram</creator><creator>Wiendl, Heinz</creator><creator>Weller, Michael</creator><general>Elsevier B.V</general><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>7T5</scope><scope>7TK</scope><scope>H94</scope></search><sort><creationdate>20050501</creationdate><title>Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system</title><author>Wischhusen, Jörg ; Schneider, Dagmar ; Mittelbronn, Michel ; Meyermann, Richard ; Engelmann, Hartmut ; Jung, Gundram ; Wiendl, Heinz ; Weller, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-fad500ced0d22484df8bc76e1f691cd07e894edcfa91b01c7638cd23343386c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amino Acid Chloromethyl Ketones - pharmacology</topic><topic>Antibodies - pharmacology</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Bispecific antibodies</topic><topic>Blotting, Northern - methods</topic><topic>Blotting, Western - methods</topic><topic>Caspases - metabolism</topic><topic>CD40</topic><topic>CD40 Antigens - immunology</topic><topic>CD40 Antigens - pharmacology</topic><topic>CD40 Antigens - physiology</topic><topic>CD40 Ligand - pharmacology</topic><topic>CD40 Ligand - physiology</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>Collagen Type XI - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Interactions</topic><topic>Fas Ligand Protein</topic><topic>fas Receptor - immunology</topic><topic>fas Receptor - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - physiology</topic><topic>Glioma</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Immunoprecipitation - methods</topic><topic>Leupeptins - pharmacology</topic><topic>Membrane Glycoproteins - pharmacology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Poly (ADP-Ribose) Polymerase-1</topic><topic>Poly(ADP-ribose) Polymerases</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>RNA Interference - physiology</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Time Factors</topic><topic>TNF-R1 (p55)</topic><topic>Transfection - methods</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wischhusen, Jörg</creatorcontrib><creatorcontrib>Schneider, Dagmar</creatorcontrib><creatorcontrib>Mittelbronn, Michel</creatorcontrib><creatorcontrib>Meyermann, Richard</creatorcontrib><creatorcontrib>Engelmann, Hartmut</creatorcontrib><creatorcontrib>Jung, Gundram</creatorcontrib><creatorcontrib>Wiendl, Heinz</creatorcontrib><creatorcontrib>Weller, Michael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wischhusen, Jörg</au><au>Schneider, Dagmar</au><au>Mittelbronn, Michel</au><au>Meyermann, Richard</au><au>Engelmann, Hartmut</au><au>Jung, Gundram</au><au>Wiendl, Heinz</au><au>Weller, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2005-05-01</date><risdate>2005</risdate><volume>162</volume><issue>1</issue><spage>28</spage><epage>42</epage><pages>28-42</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-α-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>15833357</pmid><doi>10.1016/j.jneuroim.2005.01.005</doi><tpages>15</tpages></addata></record> |
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subjects | Amino Acid Chloromethyl Ketones - pharmacology Antibodies - pharmacology Antineoplastic Agents - pharmacology Apoptosis Apoptosis - physiology Bispecific antibodies Blotting, Northern - methods Blotting, Western - methods Caspases - metabolism CD40 CD40 Antigens - immunology CD40 Antigens - pharmacology CD40 Antigens - physiology CD40 Ligand - pharmacology CD40 Ligand - physiology Cell Line, Tumor Cell Survival - drug effects Cell Survival - physiology Collagen Type XI - metabolism Dose-Response Relationship, Drug Drug Interactions Fas Ligand Protein fas Receptor - immunology fas Receptor - metabolism Gene Expression Regulation - drug effects Gene Expression Regulation - physiology Glioma Glioma - metabolism Glioma - pathology Humans Immunohistochemistry - methods Immunoprecipitation - methods Leupeptins - pharmacology Membrane Glycoproteins - pharmacology Neuroprotective Agents - pharmacology Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases Reverse Transcriptase Polymerase Chain Reaction - methods RNA Interference - physiology RNA, Messenger - biosynthesis Time Factors TNF-R1 (p55) Transfection - methods Tumor Necrosis Factor-alpha - metabolism Tumor Necrosis Factor-alpha - pharmacology |
title | Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system |
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