From Extracellular to Intracellular Targets, Inhibiting MAP Kinases in Treatment of Crohn's Disease
: In recent years the emphasis in finding new therapeutic options for chronic inflammatory diseases has been on targeting extracellular mediators of inflammation. A range of tools has become available to interfere with signaling by cytokines and their receptors. As our understanding of the intracell...
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| Veröffentlicht in: | Annals of the New York Academy of Sciences 2002-11, Vol.973 (1), p.349-358 |
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| container_title | Annals of the New York Academy of Sciences |
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| creator | VAN DEN BLINK, BERNT ten HOVE, TESSA VAN DEN BRINK, GIJS R. PEPPELENBOSCH, MAIKEL P. VAN DEVENTER, SANDER J.H. |
| description | : In recent years the emphasis in finding new therapeutic options for chronic inflammatory diseases has been on targeting extracellular mediators of inflammation. A range of tools has become available to interfere with signaling by cytokines and their receptors. As our understanding of the intracellular pathways that mediate inflammatory signals expands, new therapeutic targets within the inflammatory cells come into sight. In this review we will discuss possible intracellular targets for treatment in Crohn's disease, a chronic relapsing inflammatory disease of the gut. Despite the encouraging results with anti‐TNF antibodies in patients with Crohn's disease, our current treatment options are still insufficient and warrant novel treatment strategies. The mitogen‐activated protein kinase (MAPK) family of signal transduction proteins is an important intracellular mediator of inflammation, and recently a MAPK inhibitor was successfully used in patients with Crohn's disease. We will discuss our current understanding of the molecular pathophysiology of Crohn's disease and also novel therapies that specifically target members of the MAPK pathway. |
| doi_str_mv | 10.1111/j.1749-6632.2002.tb04664.x |
| format | Article |
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A range of tools has become available to interfere with signaling by cytokines and their receptors. As our understanding of the intracellular pathways that mediate inflammatory signals expands, new therapeutic targets within the inflammatory cells come into sight. In this review we will discuss possible intracellular targets for treatment in Crohn's disease, a chronic relapsing inflammatory disease of the gut. Despite the encouraging results with anti‐TNF antibodies in patients with Crohn's disease, our current treatment options are still insufficient and warrant novel treatment strategies. The mitogen‐activated protein kinase (MAPK) family of signal transduction proteins is an important intracellular mediator of inflammation, and recently a MAPK inhibitor was successfully used in patients with Crohn's disease. We will discuss our current understanding of the molecular pathophysiology of Crohn's disease and also novel therapies that specifically target members of the MAPK pathway.</description><subject>Crohn Disease - drug therapy</subject><subject>Crohn Disease - enzymology</subject><subject>Crohn's disease</subject><subject>cytokines</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Extracellular Space - physiology</subject><subject>human</subject><subject>Humans</subject><subject>inflammation</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-12 - physiology</subject><subject>Interleukin-18 - physiology</subject><subject>Intracellular Fluid - physiology</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>mitogen-activated protein kinases</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Models, Biological</subject><subject>Th1/Th2 cells</subject><subject>therapy</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><issn>0077-8923</issn><issn>1749-6632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE9PGzEQxa2KCtLAV6gsDvTS3Xptx97lgqJAUtRAqRqEysXy7s6Cw_5JbUeEb49XiSjXzmWkmfeePT-EjhMSJ6G-LeNE8iwSgtGYEkJjnxMuBI83H9DgbbWHBoRIGaUZZQfok3NLQhKacrmPDhLK01FYDFAxtV2DLzbe6gLqel1ri32HL9v3g4W2D-Dd1zB-NLnxpn3AV-Mb_MO02oHDpsULC9o30HrcVXhiu8f2i8PnxkEQHKKPla4dHO36EN1OLxaT79H85-xyMp5HBZejLAII3xNM6nzESKpZkpAizUDqMuVlKWTJKlEQTqFipcjDJSSTUFFRpDrPc8HYEJ1sc1e2-7sG51VjXH-EbqFbOyWpFDL4gvB0Kyxs55yFSq2sabR9UQlRPWK1VD1H1XNUPWK1Q6w2wfx598o6b6D8Z90xDYKzreDZ1PDyH9Hq-s_4N-NZSIi2CcZ52LwlaPukhGRypO6uZ2p-Q6e_FtNzdc9eATbTm7g</recordid><startdate>200211</startdate><enddate>200211</enddate><creator>VAN DEN BLINK, BERNT</creator><creator>ten HOVE, TESSA</creator><creator>VAN DEN BRINK, GIJS R.</creator><creator>PEPPELENBOSCH, MAIKEL P.</creator><creator>VAN DEVENTER, SANDER J.H.</creator><general>Blackwell Publishing Ltd</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>7X8</scope></search><sort><creationdate>200211</creationdate><title>From Extracellular to Intracellular Targets, Inhibiting MAP Kinases in Treatment of Crohn's Disease</title><author>VAN DEN BLINK, BERNT ; ten HOVE, TESSA ; VAN DEN BRINK, GIJS R. ; PEPPELENBOSCH, MAIKEL P. ; VAN DEVENTER, SANDER J.H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4759-ee128637ab5308a3110c89e7ad84dd67d3f6c042ef3d6b284097ef26c8abbb633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Crohn Disease - drug therapy</topic><topic>Crohn Disease - enzymology</topic><topic>Crohn's disease</topic><topic>cytokines</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Extracellular Space - physiology</topic><topic>human</topic><topic>Humans</topic><topic>inflammation</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-12 - physiology</topic><topic>Interleukin-18 - physiology</topic><topic>Intracellular Fluid - physiology</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>mitogen-activated protein kinases</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Models, Biological</topic><topic>Th1/Th2 cells</topic><topic>therapy</topic><topic>Tumor Necrosis Factor-alpha - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VAN DEN BLINK, BERNT</creatorcontrib><creatorcontrib>ten HOVE, TESSA</creatorcontrib><creatorcontrib>VAN DEN BRINK, GIJS R.</creatorcontrib><creatorcontrib>PEPPELENBOSCH, MAIKEL P.</creatorcontrib><creatorcontrib>VAN DEVENTER, SANDER J.H.</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>MEDLINE - Academic</collection><jtitle>Annals of the New York Academy of Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VAN DEN BLINK, BERNT</au><au>ten HOVE, TESSA</au><au>VAN DEN BRINK, GIJS R.</au><au>PEPPELENBOSCH, MAIKEL P.</au><au>VAN DEVENTER, SANDER J.H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From Extracellular to Intracellular Targets, Inhibiting MAP Kinases in Treatment of Crohn's Disease</atitle><jtitle>Annals of the New York Academy of Sciences</jtitle><addtitle>Ann N Y Acad Sci</addtitle><date>2002-11</date><risdate>2002</risdate><volume>973</volume><issue>1</issue><spage>349</spage><epage>358</epage><pages>349-358</pages><issn>0077-8923</issn><eissn>1749-6632</eissn><abstract>: In recent years the emphasis in finding new therapeutic options for chronic inflammatory diseases has been on targeting extracellular mediators of inflammation. 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| ispartof | Annals of the New York Academy of Sciences, 2002-11, Vol.973 (1), p.349-358 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Crohn Disease - drug therapy Crohn Disease - enzymology Crohn's disease cytokines Enzyme Inhibitors - therapeutic use Extracellular Space - physiology human Humans inflammation Interferon-gamma - biosynthesis Interleukin-12 - physiology Interleukin-18 - physiology Intracellular Fluid - physiology MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology mitogen-activated protein kinases Mitogen-Activated Protein Kinases - antagonists & inhibitors Models, Biological Th1/Th2 cells therapy Tumor Necrosis Factor-alpha - physiology |
| title | From Extracellular to Intracellular Targets, Inhibiting MAP Kinases in Treatment of Crohn's Disease |
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