Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions
: Although fumaric acid esters (FAE) have a decade‐long firm place in the therapeutic armamentarium for psoriasis, their pleiotropic mode of action is not yet fully understood. While most previous studies have focused on the effects of FAE on leucocytes, we have addressed their activity on macro‐ a...
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| Veröffentlicht in: | Experimental dermatology 2011-12, Vol.20 (12), p.980-985 |
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| creator | Wallbrecht, Katrin Drick, Nora Hund, Anna-Carina Schön, Michael P. |
| description | : Although fumaric acid esters (FAE) have a decade‐long firm place in the therapeutic armamentarium for psoriasis, their pleiotropic mode of action is not yet fully understood. While most previous studies have focused on the effects of FAE on leucocytes, we have addressed their activity on macro‐ and microvascular endothelial cells. As detected both on mRNA and protein levels, dimethylfumarate effected a profound reduction of TNFα‐induced expression of E‐selectin (CD62E), ICAM‐1 (CD54) and VCAM‐1 (CD106) on two different endothelial cell populations in a concentration‐dependent manner. This reduction of several endothelial adhesion molecules was accompanied by a dramatic diminution of both rolling and firm adhesive interactions between endothelial cells and lymphocytes in a dynamic flow chamber system. Dimethylfumarate, at a concentration of 50 μm, reduced lymphocyte rolling on endothelial cells by 85.9% (P |
| doi_str_mv | 10.1111/j.1600-0625.2011.01376.x |
| format | Article |
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While most previous studies have focused on the effects of FAE on leucocytes, we have addressed their activity on macro‐ and microvascular endothelial cells. As detected both on mRNA and protein levels, dimethylfumarate effected a profound reduction of TNFα‐induced expression of E‐selectin (CD62E), ICAM‐1 (CD54) and VCAM‐1 (CD106) on two different endothelial cell populations in a concentration‐dependent manner. This reduction of several endothelial adhesion molecules was accompanied by a dramatic diminution of both rolling and firm adhesive interactions between endothelial cells and lymphocytes in a dynamic flow chamber system. Dimethylfumarate, at a concentration of 50 μm, reduced lymphocyte rolling on endothelial cells by 85.9% (P < 0.001 compared to untreated controls), and it diminished the number of adherent cells by 88% (P < 0.001). In contrast, monomethylfumarate (MMF) influenced neither surface expression of adhesion molecules nor interactions between endothelial cells and lymphocytes. These observations demonstrate that endothelial cells, in addition to the known effects on leucocytes, undergo profound functional changes in response to dimethylfumarate. These changes are accompanied by severely impaired dynamic interactions with lymphocytes, which constitute the critical initial step of leucocyte recruitment to inflamed tissues in psoriasis and other TNF‐related inflammatory disorders.</description><identifier>ISSN: 0906-6705</identifier><identifier>EISSN: 1600-0625</identifier><identifier>DOI: 10.1111/j.1600-0625.2011.01376.x</identifier><identifier>PMID: 21995308</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adherent cells ; Biological and medical sciences ; Cell adhesion ; Cell Adhesion - drug effects ; Cell Adhesion - physiology ; Cell adhesion molecules ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - metabolism ; Cell interactions ; Cell Line, Transformed ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Dermatology ; Dimethyl Fumarate ; Down-Regulation - genetics ; E-selectin ; E-Selectin - genetics ; E-Selectin - metabolism ; Endothelial cells ; Endothelial Cells - cytology ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Esters ; Fumarates - pharmacology ; Fumaric acid ; fumaric acid esters ; Gene Expression - drug effects ; Gene Expression - genetics ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation ; Inflammatory diseases ; intercellular adhesion molecule 1 ; Intercellular Adhesion Molecule-1 - genetics ; Intercellular Adhesion Molecule-1 - metabolism ; Leukocyte migration ; Leukocyte Rolling - drug effects ; Leukocyte Rolling - physiology ; Leukocytes ; lymphocyte recruitment ; Lymphocytes ; Lymphocytes - cytology ; Maleates - pharmacology ; Medical sciences ; Microvasculature ; mRNA ; Psoriasis ; Psoriasis. Parapsoriasis. Lichen ; Tumor Necrosis Factor-alpha - pharmacology ; vascular cell adhesion molecule 1 ; Vascular Cell Adhesion Molecule-1 - genetics ; Vascular Cell Adhesion Molecule-1 - metabolism ; Vascular Endothelial Growth Factor A - genetics</subject><ispartof>Experimental dermatology, 2011-12, Vol.20 (12), p.980-985</ispartof><rights>2011 John Wiley & Sons A/S</rights><rights>2015 INIST-CNRS</rights><rights>2011 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4206-dcaf9b4bcbfa52f15946228ddc50de915808bf32f899b41bcd2a2ddebd55be9b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1600-0625.2011.01376.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1600-0625.2011.01376.x$$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=25245527$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21995308$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wallbrecht, Katrin</creatorcontrib><creatorcontrib>Drick, Nora</creatorcontrib><creatorcontrib>Hund, Anna-Carina</creatorcontrib><creatorcontrib>Schön, Michael P.</creatorcontrib><title>Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions</title><title>Experimental dermatology</title><addtitle>Exp Dermatol</addtitle><description>: Although fumaric acid esters (FAE) have a decade‐long firm place in the therapeutic armamentarium for psoriasis, their pleiotropic mode of action is not yet fully understood. While most previous studies have focused on the effects of FAE on leucocytes, we have addressed their activity on macro‐ and microvascular endothelial cells. As detected both on mRNA and protein levels, dimethylfumarate effected a profound reduction of TNFα‐induced expression of E‐selectin (CD62E), ICAM‐1 (CD54) and VCAM‐1 (CD106) on two different endothelial cell populations in a concentration‐dependent manner. This reduction of several endothelial adhesion molecules was accompanied by a dramatic diminution of both rolling and firm adhesive interactions between endothelial cells and lymphocytes in a dynamic flow chamber system. Dimethylfumarate, at a concentration of 50 μm, reduced lymphocyte rolling on endothelial cells by 85.9% (P < 0.001 compared to untreated controls), and it diminished the number of adherent cells by 88% (P < 0.001). In contrast, monomethylfumarate (MMF) influenced neither surface expression of adhesion molecules nor interactions between endothelial cells and lymphocytes. These observations demonstrate that endothelial cells, in addition to the known effects on leucocytes, undergo profound functional changes in response to dimethylfumarate. These changes are accompanied by severely impaired dynamic interactions with lymphocytes, which constitute the critical initial step of leucocyte recruitment to inflamed tissues in psoriasis and other TNF‐related inflammatory disorders.</description><subject>Adherent cells</subject><subject>Biological and medical sciences</subject><subject>Cell adhesion</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Adhesion - physiology</subject><subject>Cell adhesion molecules</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell interactions</subject><subject>Cell Line, Transformed</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Dermatology</subject><subject>Dimethyl Fumarate</subject><subject>Down-Regulation - genetics</subject><subject>E-selectin</subject><subject>E-Selectin - genetics</subject><subject>E-Selectin - metabolism</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Esters</subject><subject>Fumarates - pharmacology</subject><subject>Fumaric acid</subject><subject>fumaric acid esters</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression - genetics</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammatory diseases</subject><subject>intercellular adhesion molecule 1</subject><subject>Intercellular Adhesion Molecule-1 - genetics</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Leukocyte migration</subject><subject>Leukocyte Rolling - drug effects</subject><subject>Leukocyte Rolling - physiology</subject><subject>Leukocytes</subject><subject>lymphocyte recruitment</subject><subject>Lymphocytes</subject><subject>Lymphocytes - cytology</subject><subject>Maleates - pharmacology</subject><subject>Medical sciences</subject><subject>Microvasculature</subject><subject>mRNA</subject><subject>Psoriasis</subject><subject>Psoriasis. Parapsoriasis. Lichen</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>vascular cell adhesion molecule 1</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ksuO0zAUhiMEYsrAKyBvECxIsJ06lwWLUTszII1gFtx2li8n1MWxS-xomvfhQYlpKYgF3tjy_52Lff4sQwQXZF6vtgWpMM5xRVlBMSEFJmVdFft72eIk3M8WuMVVXtWYnWWPQthiTOqyZg-zM0ralpW4WWQ_1v7ODfB1tCIa75DvEDjt4wasERYJvYGQ7ntvQY0WApIT0qaHuJlsN_ZiEBFeIjlG5HycMef_1YTTyPQ7YYYeXEwV9OREbxSyU7_beDVFyP8uqsBaZFyEQajUVHicPeiEDfDkuJ9nH68uP6ze5Dfvr9-uLm5ytaTzS7USXSuXUslOMNoR1i4rShutFcMaWsIa3MiupF3TzhiRSlNBtQapGZPQyvI8e37Iuxv89xFC5L0JqRvhwI-Bt5hVddPWy5l88V-SYIqbsqmqekafHtFR9qD5bjDzz0z89wxm4NkREEEJ2w3CKRP-cIwuGaMp0esDd2csTCedYJ48wbc8jZ6n0fPkCf7LE3zPL7-s02mOzw_xJkTYn-LF8I1XyRf887trviL0lq1vP_Gr8if_4b6q</recordid><startdate>201112</startdate><enddate>201112</enddate><creator>Wallbrecht, Katrin</creator><creator>Drick, Nora</creator><creator>Hund, Anna-Carina</creator><creator>Schön, Michael P.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201112</creationdate><title>Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions</title><author>Wallbrecht, Katrin ; Drick, Nora ; Hund, Anna-Carina ; Schön, Michael P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4206-dcaf9b4bcbfa52f15946228ddc50de915808bf32f899b41bcd2a2ddebd55be9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adherent cells</topic><topic>Biological and medical sciences</topic><topic>Cell adhesion</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Adhesion - physiology</topic><topic>Cell adhesion molecules</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell interactions</topic><topic>Cell Line, Transformed</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Dermatology</topic><topic>Dimethyl Fumarate</topic><topic>Down-Regulation - genetics</topic><topic>E-selectin</topic><topic>E-Selectin - genetics</topic><topic>E-Selectin - metabolism</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Esters</topic><topic>Fumarates - pharmacology</topic><topic>Fumaric acid</topic><topic>fumaric acid esters</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression - genetics</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammatory diseases</topic><topic>intercellular adhesion molecule 1</topic><topic>Intercellular Adhesion Molecule-1 - genetics</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Leukocyte migration</topic><topic>Leukocyte Rolling - drug effects</topic><topic>Leukocyte Rolling - physiology</topic><topic>Leukocytes</topic><topic>lymphocyte recruitment</topic><topic>Lymphocytes</topic><topic>Lymphocytes - cytology</topic><topic>Maleates - pharmacology</topic><topic>Medical sciences</topic><topic>Microvasculature</topic><topic>mRNA</topic><topic>Psoriasis</topic><topic>Psoriasis. Parapsoriasis. Lichen</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>vascular cell adhesion molecule 1</topic><topic>Vascular Cell Adhesion Molecule-1 - genetics</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wallbrecht, Katrin</creatorcontrib><creatorcontrib>Drick, Nora</creatorcontrib><creatorcontrib>Hund, Anna-Carina</creatorcontrib><creatorcontrib>Schön, Michael P.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wallbrecht, Katrin</au><au>Drick, Nora</au><au>Hund, Anna-Carina</au><au>Schön, Michael P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions</atitle><jtitle>Experimental dermatology</jtitle><addtitle>Exp Dermatol</addtitle><date>2011-12</date><risdate>2011</risdate><volume>20</volume><issue>12</issue><spage>980</spage><epage>985</epage><pages>980-985</pages><issn>0906-6705</issn><eissn>1600-0625</eissn><abstract>: Although fumaric acid esters (FAE) have a decade‐long firm place in the therapeutic armamentarium for psoriasis, their pleiotropic mode of action is not yet fully understood. While most previous studies have focused on the effects of FAE on leucocytes, we have addressed their activity on macro‐ and microvascular endothelial cells. As detected both on mRNA and protein levels, dimethylfumarate effected a profound reduction of TNFα‐induced expression of E‐selectin (CD62E), ICAM‐1 (CD54) and VCAM‐1 (CD106) on two different endothelial cell populations in a concentration‐dependent manner. This reduction of several endothelial adhesion molecules was accompanied by a dramatic diminution of both rolling and firm adhesive interactions between endothelial cells and lymphocytes in a dynamic flow chamber system. Dimethylfumarate, at a concentration of 50 μm, reduced lymphocyte rolling on endothelial cells by 85.9% (P < 0.001 compared to untreated controls), and it diminished the number of adherent cells by 88% (P < 0.001). In contrast, monomethylfumarate (MMF) influenced neither surface expression of adhesion molecules nor interactions between endothelial cells and lymphocytes. These observations demonstrate that endothelial cells, in addition to the known effects on leucocytes, undergo profound functional changes in response to dimethylfumarate. These changes are accompanied by severely impaired dynamic interactions with lymphocytes, which constitute the critical initial step of leucocyte recruitment to inflamed tissues in psoriasis and other TNF‐related inflammatory disorders.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21995308</pmid><doi>10.1111/j.1600-0625.2011.01376.x</doi><tpages>6</tpages></addata></record> |
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| ispartof | Experimental dermatology, 2011-12, Vol.20 (12), p.980-985 |
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| subjects | Adherent cells Biological and medical sciences Cell adhesion Cell Adhesion - drug effects Cell Adhesion - physiology Cell adhesion molecules Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Cell interactions Cell Line, Transformed Cell Membrane - drug effects Cell Membrane - metabolism Dermatology Dimethyl Fumarate Down-Regulation - genetics E-selectin E-Selectin - genetics E-Selectin - metabolism Endothelial cells Endothelial Cells - cytology Endothelial Cells - drug effects Endothelial Cells - metabolism Esters Fumarates - pharmacology Fumaric acid fumaric acid esters Gene Expression - drug effects Gene Expression - genetics Human Umbilical Vein Endothelial Cells Humans Inflammation Inflammatory diseases intercellular adhesion molecule 1 Intercellular Adhesion Molecule-1 - genetics Intercellular Adhesion Molecule-1 - metabolism Leukocyte migration Leukocyte Rolling - drug effects Leukocyte Rolling - physiology Leukocytes lymphocyte recruitment Lymphocytes Lymphocytes - cytology Maleates - pharmacology Medical sciences Microvasculature mRNA Psoriasis Psoriasis. Parapsoriasis. Lichen Tumor Necrosis Factor-alpha - pharmacology vascular cell adhesion molecule 1 Vascular Cell Adhesion Molecule-1 - genetics Vascular Cell Adhesion Molecule-1 - metabolism Vascular Endothelial Growth Factor A - genetics |
| title | Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions |
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