VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid
Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the...
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| Veröffentlicht in: | Molecular immunology 2009-10, Vol.46 (16), p.3183-3187 |
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| creator | Peric, Mark Koglin, Sarah Dombrowski, Yvonne Groß, Kathrin Bradac, Eva Ruzicka, Thomas Schauber, Jürgen |
| description | Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out
in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression. |
| doi_str_mv | 10.1016/j.molimm.2009.08.010 |
| format | Article |
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in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/j.molimm.2009.08.010</identifier><identifier>PMID: 19733911</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>1,25-Dihydroxyvitamin D3 ; Antimicrobial Cationic Peptides - biosynthesis ; Antimicrobial Cationic Peptides - immunology ; Antimicrobial peptide ; Caco-2 Cells ; Calcitriol - pharmacology ; Calcitriol - therapeutic use ; Cathelicidin ; Detergents - pharmacology ; Detergents - therapeutic use ; Enzyme Activation - drug effects ; Enzyme Activation - immunology ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - immunology ; Humans ; Keratinocytes - immunology ; Keratinocytes - metabolism ; Lithocholic acid ; Lithocholic Acid - pharmacology ; Lithocholic Acid - therapeutic use ; MAP Kinase Kinase Kinases - immunology ; MAP Kinase Kinase Kinases - metabolism ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - immunology ; RNA, Messenger - biosynthesis ; RNA, Messenger - immunology ; RNA, Messenger - isolation & purification ; Skin Diseases - drug therapy ; Skin Diseases - immunology ; Skin Diseases - metabolism ; Vitamins - pharmacology ; Vitamins - therapeutic use</subject><ispartof>Molecular immunology, 2009-10, Vol.46 (16), p.3183-3187</ispartof><rights>2009 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-4cdd7c75cda104f7c10fb3a2646c4760b656a41b37529036f0c2a24c109c3ff23</citedby><cites>FETCH-LOGICAL-c391t-4cdd7c75cda104f7c10fb3a2646c4760b656a41b37529036f0c2a24c109c3ff23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molimm.2009.08.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19733911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peric, Mark</creatorcontrib><creatorcontrib>Koglin, Sarah</creatorcontrib><creatorcontrib>Dombrowski, Yvonne</creatorcontrib><creatorcontrib>Groß, Kathrin</creatorcontrib><creatorcontrib>Bradac, Eva</creatorcontrib><creatorcontrib>Ruzicka, Thomas</creatorcontrib><creatorcontrib>Schauber, Jürgen</creatorcontrib><title>VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid</title><title>Molecular immunology</title><addtitle>Mol Immunol</addtitle><description>Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out
in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.</description><subject>1,25-Dihydroxyvitamin D3</subject><subject>Antimicrobial Cationic Peptides - biosynthesis</subject><subject>Antimicrobial Cationic Peptides - immunology</subject><subject>Antimicrobial peptide</subject><subject>Caco-2 Cells</subject><subject>Calcitriol - pharmacology</subject><subject>Calcitriol - therapeutic use</subject><subject>Cathelicidin</subject><subject>Detergents - pharmacology</subject><subject>Detergents - therapeutic use</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - immunology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - immunology</subject><subject>Humans</subject><subject>Keratinocytes - immunology</subject><subject>Keratinocytes - metabolism</subject><subject>Lithocholic acid</subject><subject>Lithocholic Acid - pharmacology</subject><subject>Lithocholic Acid - therapeutic use</subject><subject>MAP Kinase Kinase Kinases - immunology</subject><subject>MAP Kinase Kinase Kinases - metabolism</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - immunology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - immunology</subject><subject>RNA, Messenger - isolation & purification</subject><subject>Skin Diseases - drug therapy</subject><subject>Skin Diseases - immunology</subject><subject>Skin Diseases - metabolism</subject><subject>Vitamins - pharmacology</subject><subject>Vitamins - therapeutic use</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2P0zAQhi0EYsvCP0DIJ24JYztxmgsS2i0f2kVIK-BqOeOJ6pI4wXaR-u_xqpW4cZrDPO98PIy9FlALEPrdoZ6Xyc9zLQH6GrY1CHjCNmLbyaoXjXzKNgUTVbvt4Yq9SOkAABp0-5xdib5Tqhdiw-LP2wdug-Nfd3fV7uGOO1opOAqZ--COmP0S-DLyvKeCZT97jMvg7cRXWrN3xNGW3uTROx9Khv-iaLMPC54yJT6c-OTzfsF9ORa5LdhL9my0U6JXl3rNfnzcfb_5XN1_-_Tl5sN9heW0XDXoXIddi84KaMYOBYyDslI3GptOw6BbbRsxqK6VPSg9Akorm4L1qMZRqmv29jx3jcvvI6VsZp-QpskGWo7JyEJKqVQBmzNYXksp0mjW6GcbT0aAeXRtDubs2jy6NrA1xXWJvbnMPw4zuX-hi9wCvD8DVL784ymahJ4CkvORMBu3-P9v-Au3BZKk</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>Peric, Mark</creator><creator>Koglin, Sarah</creator><creator>Dombrowski, Yvonne</creator><creator>Groß, Kathrin</creator><creator>Bradac, Eva</creator><creator>Ruzicka, Thomas</creator><creator>Schauber, Jürgen</creator><general>Elsevier Ltd</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>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>20091001</creationdate><title>VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid</title><author>Peric, Mark ; Koglin, Sarah ; Dombrowski, Yvonne ; Groß, Kathrin ; Bradac, Eva ; Ruzicka, Thomas ; Schauber, Jürgen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-4cdd7c75cda104f7c10fb3a2646c4760b656a41b37529036f0c2a24c109c3ff23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>1,25-Dihydroxyvitamin D3</topic><topic>Antimicrobial Cationic Peptides - biosynthesis</topic><topic>Antimicrobial Cationic Peptides - immunology</topic><topic>Antimicrobial peptide</topic><topic>Caco-2 Cells</topic><topic>Calcitriol - pharmacology</topic><topic>Calcitriol - therapeutic use</topic><topic>Cathelicidin</topic><topic>Detergents - pharmacology</topic><topic>Detergents - therapeutic use</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Activation - immunology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - immunology</topic><topic>Humans</topic><topic>Keratinocytes - immunology</topic><topic>Keratinocytes - metabolism</topic><topic>Lithocholic acid</topic><topic>Lithocholic Acid - pharmacology</topic><topic>Lithocholic Acid - therapeutic use</topic><topic>MAP Kinase Kinase Kinases - immunology</topic><topic>MAP Kinase Kinase Kinases - metabolism</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - immunology</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - immunology</topic><topic>RNA, Messenger - isolation & purification</topic><topic>Skin Diseases - drug therapy</topic><topic>Skin Diseases - immunology</topic><topic>Skin Diseases - metabolism</topic><topic>Vitamins - pharmacology</topic><topic>Vitamins - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peric, Mark</creatorcontrib><creatorcontrib>Koglin, Sarah</creatorcontrib><creatorcontrib>Dombrowski, Yvonne</creatorcontrib><creatorcontrib>Groß, Kathrin</creatorcontrib><creatorcontrib>Bradac, Eva</creatorcontrib><creatorcontrib>Ruzicka, Thomas</creatorcontrib><creatorcontrib>Schauber, Jürgen</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>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peric, Mark</au><au>Koglin, Sarah</au><au>Dombrowski, Yvonne</au><au>Groß, Kathrin</au><au>Bradac, Eva</au><au>Ruzicka, Thomas</au><au>Schauber, Jürgen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid</atitle><jtitle>Molecular immunology</jtitle><addtitle>Mol Immunol</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>46</volume><issue>16</issue><spage>3183</spage><epage>3187</epage><pages>3183-3187</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><abstract>Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out
in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19733911</pmid><doi>10.1016/j.molimm.2009.08.010</doi><tpages>5</tpages></addata></record> |
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| subjects | 1,25-Dihydroxyvitamin D3 Antimicrobial Cationic Peptides - biosynthesis Antimicrobial Cationic Peptides - immunology Antimicrobial peptide Caco-2 Cells Calcitriol - pharmacology Calcitriol - therapeutic use Cathelicidin Detergents - pharmacology Detergents - therapeutic use Enzyme Activation - drug effects Enzyme Activation - immunology Gene Expression Regulation - drug effects Gene Expression Regulation - immunology Humans Keratinocytes - immunology Keratinocytes - metabolism Lithocholic acid Lithocholic Acid - pharmacology Lithocholic Acid - therapeutic use MAP Kinase Kinase Kinases - immunology MAP Kinase Kinase Kinases - metabolism MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - immunology RNA, Messenger - biosynthesis RNA, Messenger - immunology RNA, Messenger - isolation & purification Skin Diseases - drug therapy Skin Diseases - immunology Skin Diseases - metabolism Vitamins - pharmacology Vitamins - therapeutic use |
| title | VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid |
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