Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells

Summary Background The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs). Objective The aim of the current study was to investigate the biological activity of iloprost on hum...

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Veröffentlicht in:Clinical and experimental allergy 2010-08, Vol.40 (8), p.1214-1221
Hauptverfasser: Müller, T., Dürk, T., Blumenthal, B., Herouy, Y., Sorichter, S., Grimm, M., Panther, E., Cicko, S., Norgauer, J., Idzko, M.
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container_end_page 1221
container_issue 8
container_start_page 1214
container_title Clinical and experimental allergy
container_volume 40
creator Müller, T.
Dürk, T.
Blumenthal, B.
Herouy, Y.
Sorichter, S.
Grimm, M.
Panther, E.
Cicko, S.
Norgauer, J.
Idzko, M.
description Summary Background The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs). Objective The aim of the current study was to investigate the biological activity of iloprost on human monocyte‐derived DCs. Methods I prostanoid (IP) receptor expression was analysed by RT‐PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co‐culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry. Results Human monocyte‐derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF‐α, IL‐6, IL‐8 and IL‐12p70 in mDCs, while it enhanced IL‐10 production. Changes in cytokine secretion were paralleled by an altered T‐cell priming capacity of DCs: in co‐culture experiments of iloprost‐treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL‐10 production. Additionally, iloprost inhibited the MIP‐3β‐induced migration of mDCs. Conclusion In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans. Cite this as: T. Müller, T. Dürk, B. Blumenthal, Y. Herouy, S. Sorichter, M. Grimm, E. Panther, S. Cicko, J. Norgauer and M. Idzko, Clinical & Experimental Allergy, 2010 (40) 1214–1221.
doi_str_mv 10.1111/j.1365-2222.2010.03558.x
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Objective The aim of the current study was to investigate the biological activity of iloprost on human monocyte‐derived DCs. Methods I prostanoid (IP) receptor expression was analysed by RT‐PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co‐culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry. Results Human monocyte‐derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF‐α, IL‐6, IL‐8 and IL‐12p70 in mDCs, while it enhanced IL‐10 production. Changes in cytokine secretion were paralleled by an altered T‐cell priming capacity of DCs: in co‐culture experiments of iloprost‐treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL‐10 production. Additionally, iloprost inhibited the MIP‐3β‐induced migration of mDCs. Conclusion In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans. Cite this as: T. Müller, T. Dürk, B. Blumenthal, Y. Herouy, S. Sorichter, M. Grimm, E. Panther, S. Cicko, J. Norgauer and M. Idzko, Clinical &amp; Experimental Allergy, 2010 (40) 1214–1221.</description><identifier>ISSN: 0954-7894</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/j.1365-2222.2010.03558.x</identifier><identifier>PMID: 20649610</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Anti-Inflammatory Agents - pharmacology ; Biological and medical sciences ; Cell Separation ; Cytokines - biosynthesis ; dendritic cells ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Forkhead Transcription Factors - biosynthesis ; FoxP3 ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; IL-10 ; iloprost ; Iloprost - pharmacology ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; Monocytes - cytology ; Monocytes - immunology ; Monocytes - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Tregs</subject><ispartof>Clinical and experimental allergy, 2010-08, Vol.40 (8), p.1214-1221</ispartof><rights>2010 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4968-f45e8ad3f891428d0c73d7a97b21d82b55c72927c044aaae07afe7eaa45c0e5c3</citedby><cites>FETCH-LOGICAL-c4968-f45e8ad3f891428d0c73d7a97b21d82b55c72927c044aaae07afe7eaa45c0e5c3</cites></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.1365-2222.2010.03558.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2222.2010.03558.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=22979870$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20649610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Müller, T.</creatorcontrib><creatorcontrib>Dürk, T.</creatorcontrib><creatorcontrib>Blumenthal, B.</creatorcontrib><creatorcontrib>Herouy, Y.</creatorcontrib><creatorcontrib>Sorichter, S.</creatorcontrib><creatorcontrib>Grimm, M.</creatorcontrib><creatorcontrib>Panther, E.</creatorcontrib><creatorcontrib>Cicko, S.</creatorcontrib><creatorcontrib>Norgauer, J.</creatorcontrib><creatorcontrib>Idzko, M.</creatorcontrib><title>Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary Background The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs). Objective The aim of the current study was to investigate the biological activity of iloprost on human monocyte‐derived DCs. Methods I prostanoid (IP) receptor expression was analysed by RT‐PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co‐culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry. Results Human monocyte‐derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF‐α, IL‐6, IL‐8 and IL‐12p70 in mDCs, while it enhanced IL‐10 production. Changes in cytokine secretion were paralleled by an altered T‐cell priming capacity of DCs: in co‐culture experiments of iloprost‐treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL‐10 production. Additionally, iloprost inhibited the MIP‐3β‐induced migration of mDCs. Conclusion In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans. Cite this as: T. Müller, T. Dürk, B. Blumenthal, Y. Herouy, S. Sorichter, M. Grimm, E. Panther, S. Cicko, J. Norgauer and M. Idzko, Clinical &amp; Experimental Allergy, 2010 (40) 1214–1221.</description><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Separation</subject><subject>Cytokines - biosynthesis</subject><subject>dendritic cells</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - biosynthesis</subject><subject>FoxP3</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>IL-10</subject><subject>iloprost</subject><subject>Iloprost - pharmacology</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>Monocytes - cytology</subject><subject>Monocytes - immunology</subject><subject>Monocytes - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Tregs</subject><issn>0954-7894</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGPEyEUxonRuHX1XzAkxuxpKjAwwMHDplm3u9moB42JF_LKMFnqDFOBavvfy9huTbzou0Dg9z0-3ocQpmROS71Zz2ndiIqVmjNSTkkthJrvHqHZ6eIxmhEteCWV5mfoWUprQgqm1VN0xkjDdUPJDH296cdNHFPG95DwZswuZAwh-8qHrodhgDzGPS7IxsXsXcJjwPfbAQIexjDafXZV66L_4VrcutBGn73F1vV9eo6edNAn9-K4nqPP764-LZbV3Yfrm8XlXWWLB1V1XDgFbd0pTTlTLbGybiVouWK0VWwlhJVMM2kJ5wDgiITOSQfAhSVO2PocXRz6FpPfty5lM_g0OYDgxm0yUvAynIayf5M1J6QhRBfy1V_ketzGUL5hqGBaEEobUih1oGyZYIquM5voB4h7Q4mZgjJrM-VhpjzMFJT5HZTZFenL4wPb1eDak_AhmQK8PgKQLPRdhGB9-sMxLbWSE_f2wP30vdv_twGzuLqcdkVfHfQ-Zbc76SF-M42spTBf3l-b2-VHuaRiaXT9C_irvYE</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Müller, T.</creator><creator>Dürk, T.</creator><creator>Blumenthal, B.</creator><creator>Herouy, Y.</creator><creator>Sorichter, S.</creator><creator>Grimm, M.</creator><creator>Panther, E.</creator><creator>Cicko, S.</creator><creator>Norgauer, J.</creator><creator>Idzko, M.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201008</creationdate><title>Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells</title><author>Müller, T. ; Dürk, T. ; Blumenthal, B. ; Herouy, Y. ; Sorichter, S. ; Grimm, M. ; Panther, E. ; Cicko, S. ; Norgauer, J. ; Idzko, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4968-f45e8ad3f891428d0c73d7a97b21d82b55c72927c044aaae07afe7eaa45c0e5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Separation</topic><topic>Cytokines - biosynthesis</topic><topic>dendritic cells</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Flow Cytometry</topic><topic>Forkhead Transcription Factors - biosynthesis</topic><topic>FoxP3</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>IL-10</topic><topic>iloprost</topic><topic>Iloprost - pharmacology</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocyte Activation - immunology</topic><topic>Monocytes - cytology</topic><topic>Monocytes - immunology</topic><topic>Monocytes - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Tregs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Müller, T.</creatorcontrib><creatorcontrib>Dürk, T.</creatorcontrib><creatorcontrib>Blumenthal, B.</creatorcontrib><creatorcontrib>Herouy, Y.</creatorcontrib><creatorcontrib>Sorichter, S.</creatorcontrib><creatorcontrib>Grimm, M.</creatorcontrib><creatorcontrib>Panther, E.</creatorcontrib><creatorcontrib>Cicko, S.</creatorcontrib><creatorcontrib>Norgauer, J.</creatorcontrib><creatorcontrib>Idzko, M.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Müller, T.</au><au>Dürk, T.</au><au>Blumenthal, B.</au><au>Herouy, Y.</au><au>Sorichter, S.</au><au>Grimm, M.</au><au>Panther, E.</au><au>Cicko, S.</au><au>Norgauer, J.</au><au>Idzko, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2010-08</date><risdate>2010</risdate><volume>40</volume><issue>8</issue><spage>1214</spage><epage>1221</epage><pages>1214-1221</pages><issn>0954-7894</issn><eissn>1365-2222</eissn><abstract>Summary Background The stable prostaglandin I2 analogue (iloprost) iloprost has been shown to inhibit allergic airway inflammation in mice by modulating the function of myeloid dendritic cells (DCs). Objective The aim of the current study was to investigate the biological activity of iloprost on human monocyte‐derived DCs. Methods I prostanoid (IP) receptor expression was analysed by RT‐PCR. Cytokine secretion by DCs and CD4+ T cells was measured by ELISA. The expression of the transcription factor FoxP3 after co‐culture of DCs with CD4+ CD45RA+ T cells was analysed by flow cytometry. Results Human monocyte‐derived DCs were found to express mRNA specific for the PGI2 receptor IP, and stimulation with iloprost resulted in increased cyclic AMP levels in both immature DCs (iDCs) and mature DCs (mDCs). Moreover, iloprost dose dependently inhibited the secretion of TNF‐α, IL‐6, IL‐8 and IL‐12p70 in mDCs, while it enhanced IL‐10 production. Changes in cytokine secretion were paralleled by an altered T‐cell priming capacity of DCs: in co‐culture experiments of iloprost‐treated mDC and naïve CD45RA+ T cells, an induction of regulatory T cells could be observed, as demonstrated by increased intracellular FoxP3 expression and IL‐10 production. Additionally, iloprost inhibited the MIP‐3β‐induced migration of mDCs. Conclusion In summary, our results provide evidence that iloprost profoundly affects the function of human myeloid DCs. Therefore, iloprost might also be a new therapeutical option for the treatment of asthma in humans. Cite this as: T. Müller, T. Dürk, B. Blumenthal, Y. Herouy, S. Sorichter, M. Grimm, E. Panther, S. Cicko, J. Norgauer and M. Idzko, Clinical &amp; Experimental Allergy, 2010 (40) 1214–1221.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20649610</pmid><doi>10.1111/j.1365-2222.2010.03558.x</doi><tpages>8</tpages></addata></record>
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subjects Anti-Inflammatory Agents - pharmacology
Biological and medical sciences
Cell Separation
Cytokines - biosynthesis
dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Forkhead Transcription Factors - biosynthesis
FoxP3
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
IL-10
iloprost
Iloprost - pharmacology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Monocytes - cytology
Monocytes - immunology
Monocytes - metabolism
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tregs
title Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells
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