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Journal of Molecular Endocrinology (2006) 37 421-432    DOI: 10.1677/jme.1.02122
© 2006 Society for Endocrinology

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17ß-Estradiol downregulates interferon regulatory factor-1 in murine splenocytes

Andrea J Lengi, Rebecca A Phillips, Ebru Karpuzoglu and Sattar Ansar Ahmed

Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Center for Molecular Medicine and Infectious Diseases, Virginia Polytechnic Institute and State University, 1410 Prices Fork Road, Blacksburg, Virginia 24061-0342, USA

(Requests for offprints should be addressed to S A Ahmed; Email: ansrahmd{at}vt.edu)

Interferon regulatory factor-1 (IRF-1) is an important transcription factor that mediates interferon-{gamma} (IFN-{gamma})-induced cell-signaling events. In this study, we examined whether 17ß-estradiol alters IRF-1 in splenic lymphocytes, in view of the immunomodulatory effects of this natural female sex hormone including its ability to alter IFN-{gamma} levels. We find that IRF-1 expression is markedly downregulated in splenocytes or purified T-cells from estrogen-treated mice at all time points studied when compared with their placebo counterparts. This decrease in IRF-1 in splenocytes from estrogen-treated mice is neither due to upregulation of IRF-1-interfering proteins (nucleophosmin or signal transducer and activator of transcription (STAT)-5) nor due to alternatively spliced IRF-1 mRNA. Given that IFN-{gamma} is a potent inducer of IRF-1, direct addition of recombinant IFN-{gamma} to splenocytes from either wild-type or IFN-{gamma}-knockout mice, or the addition of recombinant IFN-{gamma} to purified T-cells, was expected to stimulate IRF-1 expression. However, robust expression of IRF-1 in cells from estrogen-treated mice was not seen, unlike what was observed in cells from placebo-treated mice. Diminished IFN-{gamma} induction of IRF-1 in cells from estrogen-treated mice was noticed despite comparable phosphorylated STAT-1 activation. These studies are the first to show that estrogen regulates IFN-{gamma}-inducible IRF-1 in lymphoid cells, a finding that may have implications to IFN-{gamma}-regulated immune and vascular diseases.




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