The Journal of Immunology, 2007, 178: 87.33.
Copyright © 2007 by The American Association of Immunologists, Inc.
Upregulation of Th1-specific transcription factors and inflammatory responses by IFNg and IL27 in splenocytes from estrogen treated mice
Ebru Karpuzoglu,
Rebecca A Phillips,
Rujuan Dai,
Andrea J Lengi and
S. Ansar Ahmed
Department of Biomedical Sciences and Pathobiology,CMMID, Virginia Polytechnic Institute and State University, 1410, Prices Fork Road, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, 24061
Abstract
Estrogen, an immunomodulator, is believed to be involved in many autoimmune inflammatory conditions. We reported that estrogen treatment of C57BL/6 mice favors the induction of Th1 responses such as secretion of IFN
. However, the mechanisms involved in response to IFN are not well known. Therefore, we investigated the molecular pathways in splenocytes from estrogen-treated mice following in vitro exposure to Th1(IFN)-inducing cytokines: IFN, IL12 and IL27. ConA activated splenocytes from estrogen treated mice induced an IFN-dependent-increase in iNOS, nitric oxide, COX2 and MCP1. In vitro addition of IFNto ConA activated splenocytes from IFN –/– mice induced iNOS and MCP1 primarily in estrogen-treated mice. Since IFN is a potent inducer of IRF1, interestingly that neither direct addition of IFN to splenocytes from wildtype or IFN –/– mice nor the addition of IFN to T cells, induced IRF1 in cells from estrogen-treated mice. Activated splenocytes from estrogen-treated mice had noticeably increased levels of the IFN-specific transcription factor T-bet, although there were no marked changes in phosphorylated STAT1. Estrogen-induced upregulation of T-bet was largely due to IFN and IL27, but not IL12. Thus, these findings contribute novel insight regarding the pro-inflammatory effects of estrogen on the immune system and may lead to novel therapeutic approaches for autoimmune diseases.
Supported by NIH grant 5RO1 AI51880.
