Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes
Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper‐1 lymphocytes. The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell tr...
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Veröffentlicht in: | Annals of neurology 2001-09, Vol.50 (3), p.349-357 |
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description | Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper‐1 lymphocytes. The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell transmigration into the brain via interference with cell adhesion, and the upregulation of anti‐inflammatory (TH2) cytokines. In the present study, a gene expression analysis of IFN‐β‐treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN‐β that are not purely anti‐inflammatory. Specifically, we addressed the effect of IFN‐β on T helper‐1 differentiation‐ or lineage markers such as the IL‐12 receptor β2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS. Both markers were significantly upregulated in vitro and in vivo under IFN‐β therapy, supporting that this cytokine exerts complex effects on the immune system. The combination of cDNA microarray and quantitative polymerase chain reaction will expand our knowledge of the immunological effects of such pleiotropic agents as IFN‐β, may provide a key to why certain patients fail to respond, and eventually influence our view of the disease pathogenesis. |
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The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell transmigration into the brain via interference with cell adhesion, and the upregulation of anti‐inflammatory (TH2) cytokines. In the present study, a gene expression analysis of IFN‐β‐treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN‐β that are not purely anti‐inflammatory. Specifically, we addressed the effect of IFN‐β on T helper‐1 differentiation‐ or lineage markers such as the IL‐12 receptor β2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS. Both markers were significantly upregulated in vitro and in vivo under IFN‐β therapy, supporting that this cytokine exerts complex effects on the immune system. The combination of cDNA microarray and quantitative polymerase chain reaction will expand our knowledge of the immunological effects of such pleiotropic agents as IFN‐β, may provide a key to why certain patients fail to respond, and eventually influence our view of the disease pathogenesis.</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.1096</identifier><identifier>PMID: 11558791</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Adjuvants, Immunologic - pharmacology ; Adjuvants, Immunologic - therapeutic use ; Biological and medical sciences ; Biomarkers - blood ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cells, Cultured ; Humans ; Immunomodulators ; Interferon-beta - pharmacology ; Interferon-beta - therapeutic use ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - metabolism ; Medical sciences ; Multiple Sclerosis, Relapsing-Remitting - blood ; Multiple Sclerosis, Relapsing-Remitting - drug therapy ; Oligonucleotide Array Sequence Analysis - methods ; Pharmacology. Drug treatments ; Receptors, CCR5 - biosynthesis ; Receptors, CCR5 - genetics ; Receptors, Interleukin - biosynthesis ; Receptors, Interleukin - genetics ; Receptors, Interleukin-12 ; RNA, Messenger - biosynthesis ; Th1 Cells - cytology ; Th1 Cells - immunology ; Th1 Cells - metabolism ; Up-Regulation - genetics ; Up-Regulation - immunology</subject><ispartof>Annals of neurology, 2001-09, Vol.50 (3), p.349-357</ispartof><rights>Copyright © 2001 Wiley‐Liss, Inc.</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3846-9372035f706176da30ce776cb6a816f12be7644b18aa453c1ab4f3dda9907d813</citedby><cites>FETCH-LOGICAL-c3846-9372035f706176da30ce776cb6a816f12be7644b18aa453c1ab4f3dda9907d813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.1096$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.1096$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1097634$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11558791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wandinger, Klaus-Peter</creatorcontrib><creatorcontrib>Stürzebecher, Claus-Steffen</creatorcontrib><creatorcontrib>Bielekova, Bibiana</creatorcontrib><creatorcontrib>Detore, Greg</creatorcontrib><creatorcontrib>Rosenwald, Andreas</creatorcontrib><creatorcontrib>Staudt, Louis M.</creatorcontrib><creatorcontrib>McFarland, Henry F.</creatorcontrib><creatorcontrib>Martin, Roland</creatorcontrib><title>Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper‐1 lymphocytes. The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell transmigration into the brain via interference with cell adhesion, and the upregulation of anti‐inflammatory (TH2) cytokines. In the present study, a gene expression analysis of IFN‐β‐treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN‐β that are not purely anti‐inflammatory. Specifically, we addressed the effect of IFN‐β on T helper‐1 differentiation‐ or lineage markers such as the IL‐12 receptor β2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS. Both markers were significantly upregulated in vitro and in vivo under IFN‐β therapy, supporting that this cytokine exerts complex effects on the immune system. The combination of cDNA microarray and quantitative polymerase chain reaction will expand our knowledge of the immunological effects of such pleiotropic agents as IFN‐β, may provide a key to why certain patients fail to respond, and eventually influence our view of the disease pathogenesis.</description><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Adjuvants, Immunologic - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cells, Cultured</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Interferon-beta - pharmacology</subject><subject>Interferon-beta - therapeutic use</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Medical sciences</subject><subject>Multiple Sclerosis, Relapsing-Remitting - blood</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, CCR5 - biosynthesis</subject><subject>Receptors, CCR5 - genetics</subject><subject>Receptors, Interleukin - biosynthesis</subject><subject>Receptors, Interleukin - genetics</subject><subject>Receptors, Interleukin-12</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Th1 Cells - cytology</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><subject>Up-Regulation - genetics</subject><subject>Up-Regulation - immunology</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEGO1DAQRS0EYpoBiRMgLxBiE3DFiZ0sWy0YkEaDkBoNO8txyjMGJw52IqYvwIE4CGfCrY6ADSuXv179qvqEPAX2ChgrX-tR56IV98gGag5FU1btfbJhXFRFDbw6I49S-sJYRoA9JGcAdd3IFjbkxy4Mk8c76oZhGcMQ-sXrOcQDRWvRzIkGS904Y7QYw1j8-pl_dFj87HIbTcZnObmUVeOXHul8i3SZIt4cfVwYj_17eot-wkih0CkF4_SMPR10_Jq1GxwxPSYPrPYJn6zvOfn09s1-9664_HDxfre9LAxvKlG0XJaM11YyAVL0mjODUgrTCd2AsFB2KEVVddBoXdXcgO4qy_tety2TfQP8nLw4-U4xfFswzWpwyaD3esSwJCWhZKJu2gy-PIEmn5ciWjVFlzc-KGDqmLnKmatj5hl9tnou3YD9X3ANOQPPV0Ano72NejQu_WPYSsGrjBUn7LvzePjvPLW92q5zV96lGe_-8DlVJSSXtbq-ulAcMvlxf60-89_uOKk2</recordid><startdate>200109</startdate><enddate>200109</enddate><creator>Wandinger, Klaus-Peter</creator><creator>Stürzebecher, Claus-Steffen</creator><creator>Bielekova, Bibiana</creator><creator>Detore, Greg</creator><creator>Rosenwald, Andreas</creator><creator>Staudt, Louis M.</creator><creator>McFarland, Henry F.</creator><creator>Martin, Roland</creator><general>John Wiley & Sons, Inc</general><general>Willey-Liss</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>200109</creationdate><title>Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes</title><author>Wandinger, Klaus-Peter ; Stürzebecher, Claus-Steffen ; Bielekova, Bibiana ; Detore, Greg ; Rosenwald, Andreas ; Staudt, Louis M. ; McFarland, Henry F. ; Martin, Roland</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3846-9372035f706176da30ce776cb6a816f12be7644b18aa453c1ab4f3dda9907d813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adjuvants, Immunologic - pharmacology</topic><topic>Adjuvants, Immunologic - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cells, Cultured</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Interferon-beta - pharmacology</topic><topic>Interferon-beta - therapeutic use</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Medical sciences</topic><topic>Multiple Sclerosis, Relapsing-Remitting - blood</topic><topic>Multiple Sclerosis, Relapsing-Remitting - drug therapy</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, CCR5 - biosynthesis</topic><topic>Receptors, CCR5 - genetics</topic><topic>Receptors, Interleukin - biosynthesis</topic><topic>Receptors, Interleukin - genetics</topic><topic>Receptors, Interleukin-12</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Th1 Cells - cytology</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><topic>Up-Regulation - genetics</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wandinger, Klaus-Peter</creatorcontrib><creatorcontrib>Stürzebecher, Claus-Steffen</creatorcontrib><creatorcontrib>Bielekova, Bibiana</creatorcontrib><creatorcontrib>Detore, Greg</creatorcontrib><creatorcontrib>Rosenwald, Andreas</creatorcontrib><creatorcontrib>Staudt, Louis M.</creatorcontrib><creatorcontrib>McFarland, Henry F.</creatorcontrib><creatorcontrib>Martin, Roland</creatorcontrib><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wandinger, Klaus-Peter</au><au>Stürzebecher, Claus-Steffen</au><au>Bielekova, Bibiana</au><au>Detore, Greg</au><au>Rosenwald, Andreas</au><au>Staudt, Louis M.</au><au>McFarland, Henry F.</au><au>Martin, Roland</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2001-09</date><risdate>2001</risdate><volume>50</volume><issue>3</issue><spage>349</spage><epage>357</epage><pages>349-357</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><coden>ANNED3</coden><abstract>Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper‐1 lymphocytes. The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell transmigration into the brain via interference with cell adhesion, and the upregulation of anti‐inflammatory (TH2) cytokines. In the present study, a gene expression analysis of IFN‐β‐treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN‐β that are not purely anti‐inflammatory. Specifically, we addressed the effect of IFN‐β on T helper‐1 differentiation‐ or lineage markers such as the IL‐12 receptor β2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS. Both markers were significantly upregulated in vitro and in vivo under IFN‐β therapy, supporting that this cytokine exerts complex effects on the immune system. The combination of cDNA microarray and quantitative polymerase chain reaction will expand our knowledge of the immunological effects of such pleiotropic agents as IFN‐β, may provide a key to why certain patients fail to respond, and eventually influence our view of the disease pathogenesis.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>11558791</pmid><doi>10.1002/ana.1096</doi><tpages>9</tpages></addata></record> |
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subjects | Adjuvants, Immunologic - pharmacology Adjuvants, Immunologic - therapeutic use Biological and medical sciences Biomarkers - blood Cell Differentiation - genetics Cell Differentiation - immunology Cells, Cultured Humans Immunomodulators Interferon-beta - pharmacology Interferon-beta - therapeutic use Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Medical sciences Multiple Sclerosis, Relapsing-Remitting - blood Multiple Sclerosis, Relapsing-Remitting - drug therapy Oligonucleotide Array Sequence Analysis - methods Pharmacology. Drug treatments Receptors, CCR5 - biosynthesis Receptors, CCR5 - genetics Receptors, Interleukin - biosynthesis Receptors, Interleukin - genetics Receptors, Interleukin-12 RNA, Messenger - biosynthesis Th1 Cells - cytology Th1 Cells - immunology Th1 Cells - metabolism Up-Regulation - genetics Up-Regulation - immunology |
title | Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes |
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