Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: Role of interferon-gamma

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dc.contributor.authorKarpuzoglu, Ebruen
dc.contributor.authorFenaux, Jillian B.en
dc.contributor.authorPhillips, Rebecca A.en
dc.contributor.authorLengi, Andrea J.en
dc.contributor.authorElvinger, Francoisen
dc.contributor.authorAhmed, Sattar Ansaren
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:17Zen
dc.date.available2014-07-08T13:02:17Zen
dc.date.issued2006-02en
dc.description.abstractEstrogen is implicated in many autoimmune diseases and is a robust immunomodulator. For example, it regulates interferon (IFN)-gamma, a cytokine believed to up-regulate inducible nitric oxide synthase (iNOS). A notable gap in the literature is a lack of information on the regulation of nitric oxide in immune tissues by estrogen. We now show that activation of splenocytes with T cell stimulants [concanavalin-A (Con-A) or anti-CD3 antibodies] results in copious release of nitric oxide in splenocyte cultures from estrogen-treated but not placebo-treated mice. Moreover, even a low dose of T cell stimulants induced nitric oxide in splenocytes from estrogen-treated, but not placebo-treated, mice. Con-A-activated splenocytes from estrogen-treated mice also have up-regulated iNOS mRNA, iNOS protein, and cyclooxygenase-2 (a nitric oxide-regulated downstream proinflammatory protein) when compared with controls. Our studies suggest that the induction of nitric oxide by activated splenocytes from estrogen-treated mice is mediated in part by IFN gamma. First, blocking costimulatory signals mediated through interactions of CD28 and B7 molecules by CTLA-4Ig markedly decreased not only IFN gamma but also nitric oxide. Second, estrogen treatment of IFN gamma-knockout (IFN gamma(-)/(-)) mice did not induce iNOS protein or nitric oxide. Finally, in vitro addition of recombinant IFN gamma to Con-A-activated splenocytes from IFN gamma((-)/(-)) mice induced iNOS protein primarily in estrogen-treated mice. Overall, this is the first report to show that estrogen treatment up-regulates IFN gamma-inducible-iNOS gene expression, iNOS protein, nitric oxide, and cyclooxygenase-2 as an indirect consequence of activation of T cells. These findings may have wide implications to immunity and inflammatory disorders including female-predominant autoimmune diseases.en
dc.description.sponsorshipNational Institutes of Health (5RO1 AI51880-03)en
dc.description.sponsorshipU.S. Department of Agriculture (USDA)-Hatchen
dc.description.sponsorshipUSDA-Animal Health and Disease programsen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationEbru Karpuzoglu, Jillian B. Fenaux, Rebecca A. Phillips, Andrea J. Lengi, François Elvinger, and S. Ansar Ahmed. "Estrogen Up-Regulates Inducible Nitric Oxide Synthase, Nitric Oxide, and Cyclooxygenase-2 in Splenocytes Activated with T Cell Stimulants: Role of Interferon-γ," Endocrinology 2006 147:2, 662-671. DOI: http://dx.doi.org/10.1210/en.2005-0829en
dc.identifier.doihttps://doi.org/10.1210/en.2005-0829en
dc.identifier.issn0013-7227en
dc.identifier.urihttp://hdl.handle.net/10919/49391en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/en.2005-0829en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectautoimmune-diseasesen
dc.subjectsex-hormonesen
dc.subjectprostaglandin e-2en
dc.subjecthuman monocytesen
dc.subjectimmune-systemen
dc.subjectreceptor-betaen
dc.subjectifn-gammaen
dc.subjectexpressionen
dc.subject17-beta-estradiolen
dc.subjectmacrophagesen
dc.subjectendocrinology & metabolismen
dc.titleEstrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: Role of interferon-gammaen
dc.title.serialEndocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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