A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis
Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the p...
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creator | Shiri-Shahsavar, Mohammad Reza Mirshafiee, Abbas Parastouei, Karim Ebrahimi-Kalan, Abbas Yekaninejad, Saeed Soleymani, Farid Chahardoli, Reza Mazaheri Nezhad Fard, Ramin Saboor-Yaraghi, Ali Akbar |
description | Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D
3
(D
3
), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D
3
, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (
p
values |
doi_str_mv | 10.1007/s12031-016-0834-4 |
format | Article |
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3
(D
3
), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D
3
, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (
p
values <0.001). Interferon γ secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (
p
= 0.004,
p
= 0.029, respectively) while PPARγ mRNA expression was significantly increased in Group T compared to Group E (
p
= 0.021). These findings highlighted that ATRA, D
3
, and DHA combination modulated PPARγ and T-bet gene expression and resulted in decrease in Th1 response and lymphocyte invasion into the central nervous system (CNS) and resultant inflammation. In conclusion, the results of this study suggested the potential use of this intervention in treatment and/or prevention of EAE/MS and probably other Th1 cell-mediated autoimmune diseases.</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1007/s12031-016-0834-4</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Neurochemistry ; Neurology ; Neurosciences ; Proteomics</subject><ispartof>Journal of molecular neuroscience, 2016-12, Vol.60 (4), p.498-508</ispartof><rights>Springer Science+Business Media New York 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2364-ff94438581095c0e7b88096c26652dc0deefd7c4cf42f7aceb7a86d48393db583</citedby><cites>FETCH-LOGICAL-c2364-ff94438581095c0e7b88096c26652dc0deefd7c4cf42f7aceb7a86d48393db583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12031-016-0834-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12031-016-0834-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Shiri-Shahsavar, Mohammad Reza</creatorcontrib><creatorcontrib>Mirshafiee, Abbas</creatorcontrib><creatorcontrib>Parastouei, Karim</creatorcontrib><creatorcontrib>Ebrahimi-Kalan, Abbas</creatorcontrib><creatorcontrib>Yekaninejad, Saeed</creatorcontrib><creatorcontrib>Soleymani, Farid</creatorcontrib><creatorcontrib>Chahardoli, Reza</creatorcontrib><creatorcontrib>Mazaheri Nezhad Fard, Ramin</creatorcontrib><creatorcontrib>Saboor-Yaraghi, Ali Akbar</creatorcontrib><title>A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><description>Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D
3
(D
3
), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D
3
, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (
p
values <0.001). Interferon γ secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (
p
= 0.004,
p
= 0.029, respectively) while PPARγ mRNA expression was significantly increased in Group T compared to Group E (
p
= 0.021). These findings highlighted that ATRA, D
3
, and DHA combination modulated PPARγ and T-bet gene expression and resulted in decrease in Th1 response and lymphocyte invasion into the central nervous system (CNS) and resultant inflammation. In conclusion, the results of this study suggested the potential use of this intervention in treatment and/or prevention of EAE/MS and probably other Th1 cell-mediated autoimmune diseases.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Proteomics</subject><issn>0895-8696</issn><issn>1559-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp9kc2O0zAUhSMEEmXgAdh5yaIGO3EcZxnamTLSCKqZso5c54Z65J9iO6P2uXgPXglchQViwerq6n7nHF2donhLyXtKSPMh0pJUFBPKMREVw-xZsaB13WJKOX9eLIhoayx4y18Wr2J8JKSkjIpF8atDn_0TGLTydq-dTNo75Ee09spHeYCTBOe1Qp3SwxJ1xuBdkC6ie0j6r4N0A6JLVNZ4rQ_nIfjT-UknabVD6yrDw6Qgoh3-CAltwAG6Ph0DxJjTlugBwmTRrUsQRgg5fyOtlbPpyminlTToQfksQPspoW3w1qe8bLfd_c8f_xqiHJo3CNqCS1naTclra6cL5RQcD9J4ewajk46vixejNBHe_JlXxdeb693qE777srlddXdYlRVneBxbxipRC0raWhFo9kKQlquS87ocFBkAxqFRTI2sHBupYN9IwQcmqrYa9rWorop3s-8x-O8TxNRbHRUYIx34KfY0kw3L5nVG6Yyq4GMMMPbH_IoM556S_lJ2P5fd57L7S9k9y5py1sTMum8Q-kc_BZc_-o_oN8XTsN4</recordid><startdate>20161201</startdate><enddate>20161201</enddate><creator>Shiri-Shahsavar, Mohammad Reza</creator><creator>Mirshafiee, Abbas</creator><creator>Parastouei, Karim</creator><creator>Ebrahimi-Kalan, Abbas</creator><creator>Yekaninejad, Saeed</creator><creator>Soleymani, Farid</creator><creator>Chahardoli, Reza</creator><creator>Mazaheri Nezhad Fard, Ramin</creator><creator>Saboor-Yaraghi, Ali Akbar</creator><general>Springer US</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20161201</creationdate><title>A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis</title><author>Shiri-Shahsavar, Mohammad Reza ; Mirshafiee, Abbas ; Parastouei, Karim ; Ebrahimi-Kalan, Abbas ; Yekaninejad, Saeed ; Soleymani, Farid ; Chahardoli, Reza ; Mazaheri Nezhad Fard, Ramin ; Saboor-Yaraghi, Ali Akbar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2364-ff94438581095c0e7b88096c26652dc0deefd7c4cf42f7aceb7a86d48393db583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Proteomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shiri-Shahsavar, Mohammad Reza</creatorcontrib><creatorcontrib>Mirshafiee, Abbas</creatorcontrib><creatorcontrib>Parastouei, Karim</creatorcontrib><creatorcontrib>Ebrahimi-Kalan, Abbas</creatorcontrib><creatorcontrib>Yekaninejad, Saeed</creatorcontrib><creatorcontrib>Soleymani, Farid</creatorcontrib><creatorcontrib>Chahardoli, Reza</creatorcontrib><creatorcontrib>Mazaheri Nezhad Fard, Ramin</creatorcontrib><creatorcontrib>Saboor-Yaraghi, Ali Akbar</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shiri-Shahsavar, Mohammad Reza</au><au>Mirshafiee, Abbas</au><au>Parastouei, Karim</au><au>Ebrahimi-Kalan, Abbas</au><au>Yekaninejad, Saeed</au><au>Soleymani, Farid</au><au>Chahardoli, Reza</au><au>Mazaheri Nezhad Fard, Ramin</au><au>Saboor-Yaraghi, Ali Akbar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis</atitle><jtitle>Journal of molecular neuroscience</jtitle><stitle>J Mol Neurosci</stitle><date>2016-12-01</date><risdate>2016</risdate><volume>60</volume><issue>4</issue><spage>498</spage><epage>508</epage><pages>498-508</pages><issn>0895-8696</issn><eissn>1559-1166</eissn><abstract>Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D
3
(D
3
), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D
3
, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (
p
values <0.001). Interferon γ secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (
p
= 0.004,
p
= 0.029, respectively) while PPARγ mRNA expression was significantly increased in Group T compared to Group E (
p
= 0.021). These findings highlighted that ATRA, D
3
, and DHA combination modulated PPARγ and T-bet gene expression and resulted in decrease in Th1 response and lymphocyte invasion into the central nervous system (CNS) and resultant inflammation. In conclusion, the results of this study suggested the potential use of this intervention in treatment and/or prevention of EAE/MS and probably other Th1 cell-mediated autoimmune diseases.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s12031-016-0834-4</doi><tpages>11</tpages></addata></record> |
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subjects | Biomedical and Life Sciences Biomedicine Cell Biology Neurochemistry Neurology Neurosciences Proteomics |
title | A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis |
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