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dc.creatorNacka-Aleksić, Mirjana
dc.creatorĐikić, Jasmina
dc.creatorPilipović, Ivan
dc.creatorStojić-Vukanić, Zorica
dc.creatorKosec, Duško
dc.creatorBufan, Biljana
dc.creatorArsenović-Ranin, Nevena
dc.creatorDimitrijević, Mirjana
dc.creatorLeposavić, Gordana
dc.date.accessioned2019-09-02T11:45:30Z
dc.date.available2019-09-02T11:45:30Z
dc.date.issued2015
dc.identifier.issn0889-1591
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2348
dc.description.abstractCompared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/-macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-gamma+:IL-1 7+IL-10+ cell ratio was shifted towards IL-17+IFN-gamma+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1 beta and IL-6, but downregulated TGF-beta mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD 134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE.en
dc.publisherAcademic Press Inc Elsevier Science, San Diego
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175050/RS//
dc.rightsrestrictedAccess
dc.sourceBrain Behavior and Immunity
dc.titleMale rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord levelen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractСтојић-Вуканић, Зорица; Лепосавић, Гордана; Пилиповић, Иван; Косец, Душко; Димитријевић, Мирјана; Aрсеновић-Ранин, Невена; Буфан, Биљана; Нацка-Aлексић, Мирјана; Ђикић, Јасмина;
dc.citation.volume49
dc.citation.spage101
dc.citation.epage118
dc.citation.other49: 101-118
dc.citation.rankM21
dc.identifier.wos000361257900014
dc.identifier.doi10.1016/j.bbi.2015.04.017
dc.identifier.pmid25944279
dc.identifier.scopus2-s2.0-84940598922
dc.identifier.rcubconv_3390
dc.type.versionpublishedVersion


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