Curcumin attenuates acute graft-versus-host disease severity via in vivo regulations on Th1, Th17 and regulatory T cells

In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model. Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated al...

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Veröffentlicht in:PloS one 2013-06, Vol.8 (6), p.e67171-e67171
Hauptverfasser: Park, Min-Jung, Moon, Su-Jin, Lee, Sung-Hee, Yang, Eun-Ji, Min, Jun-Ki, Cho, Seok-Goo, Yang, Chul-Woo, Park, Sung-Hwan, Kim, Ho-Youn, Cho, Mi-La
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container_title PloS one
container_volume 8
creator Park, Min-Jung
Moon, Su-Jin
Lee, Sung-Hee
Yang, Eun-Ji
Min, Jun-Ki
Cho, Seok-Goo
Yang, Chul-Woo
Park, Sung-Hwan
Kim, Ho-Youn
Cho, Mi-La
description In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model. Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations. In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.
doi_str_mv 10.1371/journal.pone.0067171
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Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations. In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067171</identifier><identifier>PMID: 23840617</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animal tissues ; Animals ; Antigens ; Apoptosis ; B-Lymphocytes - drug effects ; B-Lymphocytes - immunology ; Biological response modifiers ; Biology ; Bone marrow ; Bone Marrow Transplantation ; c-Fos protein ; c-Jun protein ; CD4 antigen ; CD8 antigen ; Cell Proliferation ; Cells, Cultured ; Colon ; Colon - drug effects ; Colon - metabolism ; Colon - pathology ; Comparative analysis ; Curcumin ; Curcumin - pharmacology ; Curcumin - therapeutic use ; Disease ; Flow cytometry ; Fos protein ; Foxp3 protein ; Gene expression ; Graft vs Host Disease - drug therapy ; Graft vs Host Disease - immunology ; Graft-versus-host reaction ; Helper cells ; Homeostasis ; Immunohistochemistry ; Immunologic Factors - pharmacology ; Immunologic Factors - therapeutic use ; Immunology ; Immunoregulation ; In vivo methods and tests ; Interferon ; Interferon-gamma - metabolism ; Interleukin-17 - metabolism ; Interleukins ; Internal medicine ; Intestine ; Liver ; Lungs ; Lymph nodes ; Lymphocyte Culture Test, Mixed ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Lymphoma ; Medicine ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Organs ; Proteins ; Rheumatism ; Rheumatology ; Science ; Skin ; Skin - drug effects ; Skin - metabolism ; Skin - pathology ; Spleen - immunology ; Spleen - pathology ; Splenocytes ; Stem cells ; Subpopulations ; T cells ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Th1 Cells - drug effects ; Th1 Cells - immunology ; Th17 Cells - drug effects ; Th17 Cells - immunology ; Transcription Factor AP-1 - antagonists &amp; inhibitors ; Transcription Factor AP-1 - metabolism ; Transcription factors ; Transplantation ; Transplants &amp; implants ; Tumor necrosis factor-TNF ; γ-Interferon</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e67171-e67171</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Park et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations. In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.</description><subject>Animal models</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - immunology</subject><subject>Biological response modifiers</subject><subject>Biology</subject><subject>Bone marrow</subject><subject>Bone Marrow Transplantation</subject><subject>c-Fos protein</subject><subject>c-Jun protein</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Colon</subject><subject>Colon - drug effects</subject><subject>Colon - metabolism</subject><subject>Colon - pathology</subject><subject>Comparative analysis</subject><subject>Curcumin</subject><subject>Curcumin - pharmacology</subject><subject>Curcumin - therapeutic use</subject><subject>Disease</subject><subject>Flow cytometry</subject><subject>Fos protein</subject><subject>Foxp3 protein</subject><subject>Gene expression</subject><subject>Graft vs Host Disease - drug therapy</subject><subject>Graft vs Host Disease - immunology</subject><subject>Graft-versus-host reaction</subject><subject>Helper cells</subject><subject>Homeostasis</subject><subject>Immunohistochemistry</subject><subject>Immunologic Factors - pharmacology</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Immunology</subject><subject>Immunoregulation</subject><subject>In vivo methods and tests</subject><subject>Interferon</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin-17 - metabolism</subject><subject>Interleukins</subject><subject>Internal medicine</subject><subject>Intestine</subject><subject>Liver</subject><subject>Lungs</subject><subject>Lymph nodes</subject><subject>Lymphocyte Culture Test, Mixed</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Organs</subject><subject>Proteins</subject><subject>Rheumatism</subject><subject>Rheumatology</subject><subject>Science</subject><subject>Skin</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Spleen - immunology</subject><subject>Spleen - pathology</subject><subject>Splenocytes</subject><subject>Stem cells</subject><subject>Subpopulations</subject><subject>T cells</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Th1 Cells - drug effects</subject><subject>Th1 Cells - immunology</subject><subject>Th17 Cells - drug effects</subject><subject>Th17 Cells - immunology</subject><subject>Transcription Factor AP-1 - antagonists &amp; inhibitors</subject><subject>Transcription Factor AP-1 - metabolism</subject><subject>Transcription factors</subject><subject>Transplantation</subject><subject>Transplants &amp; implants</subject><subject>Tumor necrosis factor-TNF</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk29r2zAQxs3YWLtu32BsgsHYYM4ky7HlN4MS9idQKGzZ3oqzfHZUHCuV5NB8-8mNU-LRF8Ngi9PvHt091kXRa0ZnjOfs843pbQftbGs6nFGa5SxnT6JzVvAkzhLKn56sz6IXzt1QOuciy55HZwkXKc1Yfh7dLXqr-o3uCHiPXQ8eHQHVeySNhdrHO7Sud_HaOE8q7RAcEochqv2e7DSQkLrTO0MsNn0LXpvOEdOR1Zp9Gl45ga46bhq7JyuisG3dy-hZDa3DV-P3Ivr97etq8SO-uv6-XFxexSorEh_XinHBawTBaqSKJ7ycl5SWFZ0DxUyVXIisFKwoGKYiRcgARJLPFc9EWRQlv4jeHnS3rXFyNM3JYCFlItiRB2J5ICoDN3Jr9QbsXhrQ8j5gbCPBeq1alFjRpMAi5cHrFEVaKkjKQqg6qThwSIPWl_G0vtxgpbDzFtqJ6HSn02vZmJ0M5YosKYLAh1HAmtsenZcb7QbDoEPTD3UXxZymeT7U_e4f9PHuRqqB0IDuahPOVYOovEzzYFzC83mgZo9Q4alwo1W4YbUO8UnCx0lCYDze-QZ65-Ty18__Z6__TNn3J-waofVrZ9r-_l5NwfQAKmucs1g_mMzo0D87uiGHAZHjgIS0N6c_6CHpOBH8L355C_0</recordid><startdate>20130620</startdate><enddate>20130620</enddate><creator>Park, Min-Jung</creator><creator>Moon, Su-Jin</creator><creator>Lee, Sung-Hee</creator><creator>Yang, Eun-Ji</creator><creator>Min, Jun-Ki</creator><creator>Cho, Seok-Goo</creator><creator>Yang, Chul-Woo</creator><creator>Park, Sung-Hwan</creator><creator>Kim, Ho-Youn</creator><creator>Cho, Mi-La</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130620</creationdate><title>Curcumin attenuates acute graft-versus-host disease severity via in vivo regulations on Th1, Th17 and regulatory T cells</title><author>Park, Min-Jung ; 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Min-Jung</au><au>Moon, Su-Jin</au><au>Lee, Sung-Hee</au><au>Yang, Eun-Ji</au><au>Min, Jun-Ki</au><au>Cho, Seok-Goo</au><au>Yang, Chul-Woo</au><au>Park, Sung-Hwan</au><au>Kim, Ho-Youn</au><au>Cho, Mi-La</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Curcumin attenuates acute graft-versus-host disease severity via in vivo regulations on Th1, Th17 and regulatory T cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-06-20</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>e67171</spage><epage>e67171</epage><pages>e67171-e67171</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model. Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations. In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23840617</pmid><doi>10.1371/journal.pone.0067171</doi><tpages>e67171</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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issn 1932-6203
1932-6203
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subjects Animal models
Animal tissues
Animals
Antigens
Apoptosis
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
Biological response modifiers
Biology
Bone marrow
Bone Marrow Transplantation
c-Fos protein
c-Jun protein
CD4 antigen
CD8 antigen
Cell Proliferation
Cells, Cultured
Colon
Colon - drug effects
Colon - metabolism
Colon - pathology
Comparative analysis
Curcumin
Curcumin - pharmacology
Curcumin - therapeutic use
Disease
Flow cytometry
Fos protein
Foxp3 protein
Gene expression
Graft vs Host Disease - drug therapy
Graft vs Host Disease - immunology
Graft-versus-host reaction
Helper cells
Homeostasis
Immunohistochemistry
Immunologic Factors - pharmacology
Immunologic Factors - therapeutic use
Immunology
Immunoregulation
In vivo methods and tests
Interferon
Interferon-gamma - metabolism
Interleukin-17 - metabolism
Interleukins
Internal medicine
Intestine
Liver
Lungs
Lymph nodes
Lymphocyte Culture Test, Mixed
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Medicine
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Organs
Proteins
Rheumatism
Rheumatology
Science
Skin
Skin - drug effects
Skin - metabolism
Skin - pathology
Spleen - immunology
Spleen - pathology
Splenocytes
Stem cells
Subpopulations
T cells
T-Lymphocytes, Regulatory - drug effects
T-Lymphocytes, Regulatory - immunology
Th1 Cells - drug effects
Th1 Cells - immunology
Th17 Cells - drug effects
Th17 Cells - immunology
Transcription Factor AP-1 - antagonists & inhibitors
Transcription Factor AP-1 - metabolism
Transcription factors
Transplantation
Transplants & implants
Tumor necrosis factor-TNF
γ-Interferon
title Curcumin attenuates acute graft-versus-host disease severity via in vivo regulations on Th1, Th17 and regulatory T cells
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