Induction of Regulatory CD4+ Cells and Prolongation of Survival of Fully Allogeneic Murine Cardiac Grafts by Danazol
Abstract Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA...
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| Veröffentlicht in: | Transplantation proceedings 2012-05, Vol.44 (4), p.1067-1069 |
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| description | Abstract Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2k ) that underwent transplantation of C57BL/6 (B6, H2b ) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4+ cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4+ CD25+ Foxp3+ cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4+ cells. |
| doi_str_mv | 10.1016/j.transproceed.2012.01.103 |
| format | Article |
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We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2k ) that underwent transplantation of C57BL/6 (B6, H2b ) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4+ cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4+ CD25+ Foxp3+ cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4+ cells.</description><identifier>ISSN: 0041-1345</identifier><identifier>EISSN: 1873-2623</identifier><identifier>DOI: 10.1016/j.transproceed.2012.01.103</identifier><identifier>PMID: 22564626</identifier><identifier>CODEN: TRPPA8</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Adoptive Transfer ; Animals ; Biological and medical sciences ; Cell Proliferation - drug effects ; Cytokines - metabolism ; Danazol - administration & dosage ; Danazol - pharmacology ; Flow Cytometry ; Forkhead Transcription Factors - metabolism ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Graft Survival - drug effects ; Heart Transplantation - immunology ; Histocompatibility ; Immunologic Factors - administration & dosage ; Immunologic Factors - pharmacology ; Injections, Intraperitoneal ; Interleukin-2 Receptor alpha Subunit - metabolism ; Lymphocyte Activation - drug effects ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - transplantation ; Time Factors ; Tissue, organ and graft immunology</subject><ispartof>Transplantation proceedings, 2012-05, Vol.44 (4), p.1067-1069</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-b0fb2fa287c858b05848aad8c1141ca61c87708066a9158380d68245ef779f513</citedby><cites>FETCH-LOGICAL-c531t-b0fb2fa287c858b05848aad8c1141ca61c87708066a9158380d68245ef779f513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.transproceed.2012.01.103$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,780,784,789,790,3550,23930,23931,25140,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25943424$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22564626$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uchiyama, M</creatorcontrib><creatorcontrib>Jin, X</creatorcontrib><creatorcontrib>Zhang, Q</creatorcontrib><creatorcontrib>Amano, A</creatorcontrib><creatorcontrib>Watanabe, T</creatorcontrib><creatorcontrib>Niimi, M</creatorcontrib><title>Induction of Regulatory CD4+ Cells and Prolongation of Survival of Fully Allogeneic Murine Cardiac Grafts by Danazol</title><title>Transplantation proceedings</title><addtitle>Transplant Proc</addtitle><description>Abstract Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2k ) that underwent transplantation of C57BL/6 (B6, H2b ) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4+ cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4+ CD25+ Foxp3+ cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4+ cells.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation - drug effects</subject><subject>Cytokines - metabolism</subject><subject>Danazol - administration & dosage</subject><subject>Danazol - pharmacology</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival - drug effects</subject><subject>Heart Transplantation - immunology</subject><subject>Histocompatibility</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Immunologic Factors - pharmacology</subject><subject>Injections, Intraperitoneal</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - transplantation</subject><subject>Time Factors</subject><subject>Tissue, organ and graft immunology</subject><issn>0041-1345</issn><issn>1873-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNklGL1DAQgIMo3rr6FyQIgiBdM0naZn0Qjq53Hpwonj6HNE2XrNnkLmkX6q83ZXdRfPIpCfPNTPJlEHoFZAUEqne71RCVT_cxaGO6FSVAVwRyjD1CCxA1K2hF2WO0IIRDAYyXF-hZSjuSz5Szp-iC0rLiFa0WaLjx3agHGzwOPf5mtqNTQ4gTbjb8LW6Mcwkr3-GvMbjgt-pM3o3xYA_Kzfur0bkJXzoXtsYbq_HnMVpvcKNiZ5XG11H1Q8LthDfKq1_BPUdPeuWSeXFal-jH1cfvzafi9sv1TXN5W-iSwVC0pG9pr6iotShFS0rBhVKd0AActKpAi7omglSVWkMpmCBdJSgvTV_X674EtkRvjnWzqofRpEHubdL5TcqbMCaZbYLgIEid0fdHVMeQUjS9vI92r-KUoZmr5E7-bV3O1iWBHGM5-eWpz9juc-ycetacgdcnQCWtXJ8LaZv-cOWas_lrlmhz5Ey2crAmyqSt8dp0Nho9yC7Y_7vPh3_KaGe9zZ1_msmkXRijz94lyJRz5N08J_OYACUEmBDsN9jJuyM</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Uchiyama, M</creator><creator>Jin, X</creator><creator>Zhang, Q</creator><creator>Amano, A</creator><creator>Watanabe, T</creator><creator>Niimi, M</creator><general>Elsevier Inc</general><general>Elsevier</general><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>20120501</creationdate><title>Induction of Regulatory CD4+ Cells and Prolongation of Survival of Fully Allogeneic Murine Cardiac Grafts by Danazol</title><author>Uchiyama, M ; Jin, X ; Zhang, Q ; Amano, A ; Watanabe, T ; Niimi, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c531t-b0fb2fa287c858b05848aad8c1141ca61c87708066a9158380d68245ef779f513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation - drug effects</topic><topic>Cytokines - metabolism</topic><topic>Danazol - administration & dosage</topic><topic>Danazol - pharmacology</topic><topic>Flow Cytometry</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival - drug effects</topic><topic>Heart Transplantation - immunology</topic><topic>Histocompatibility</topic><topic>Immunologic Factors - administration & dosage</topic><topic>Immunologic Factors - pharmacology</topic><topic>Injections, Intraperitoneal</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CBA</topic><topic>Surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - transplantation</topic><topic>Time Factors</topic><topic>Tissue, organ and graft immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uchiyama, M</creatorcontrib><creatorcontrib>Jin, X</creatorcontrib><creatorcontrib>Zhang, Q</creatorcontrib><creatorcontrib>Amano, A</creatorcontrib><creatorcontrib>Watanabe, T</creatorcontrib><creatorcontrib>Niimi, M</creatorcontrib><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>Transplantation proceedings</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uchiyama, M</au><au>Jin, X</au><au>Zhang, Q</au><au>Amano, A</au><au>Watanabe, T</au><au>Niimi, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of Regulatory CD4+ Cells and Prolongation of Survival of Fully Allogeneic Murine Cardiac Grafts by Danazol</atitle><jtitle>Transplantation proceedings</jtitle><addtitle>Transplant Proc</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>44</volume><issue>4</issue><spage>1067</spage><epage>1069</epage><pages>1067-1069</pages><issn>0041-1345</issn><eissn>1873-2623</eissn><coden>TRPPA8</coden><abstract>Abstract Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2k ) that underwent transplantation of C57BL/6 (B6, H2b ) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4+ cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4+ CD25+ Foxp3+ cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4+ cells.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22564626</pmid><doi>10.1016/j.transproceed.2012.01.103</doi><tpages>3</tpages></addata></record> |
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| ispartof | Transplantation proceedings, 2012-05, Vol.44 (4), p.1067-1069 |
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| subjects | Adoptive Transfer Animals Biological and medical sciences Cell Proliferation - drug effects Cytokines - metabolism Danazol - administration & dosage Danazol - pharmacology Flow Cytometry Forkhead Transcription Factors - metabolism Fundamental and applied biological sciences. Psychology Fundamental immunology Graft Rejection - immunology Graft Rejection - prevention & control Graft Survival - drug effects Heart Transplantation - immunology Histocompatibility Immunologic Factors - administration & dosage Immunologic Factors - pharmacology Injections, Intraperitoneal Interleukin-2 Receptor alpha Subunit - metabolism Lymphocyte Activation - drug effects Male Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred CBA Surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - transplantation Time Factors Tissue, organ and graft immunology |
| title | Induction of Regulatory CD4+ Cells and Prolongation of Survival of Fully Allogeneic Murine Cardiac Grafts by Danazol |
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