Upregulation of Th1-specific transcription factors and inflammatory responses by IFNg and IL27 in splenocytes from estrogen treated mice (87.33)

Abstract

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 IFNγ. However, the mechanisms involved in response to IFNγ are not well known. Therefore, we investigated the molecular pathways in splenocytes from estrogen-treated mice following in vitro exposure to Th1(IFNγ)-inducing cytokines: IFNγ, IL12 and IL27. ConA activated splenocytes from estrogen treated mice induced an IFNγ-dependent-increase in iNOS, nitric oxide, COX2 and MCP1. In vitro addition of IFNγto ConA activated splenocytes from IFNγ −/− mice induced iNOS and MCP1 primarily in estrogen-treated mice. Since IFNγ is a potent inducer of IRF1, interestingly that neither direct addition of IFNγ to splenocytes from wildtype or IFNγ −/− mice nor the addition of IFNγ to T cells, induced IRF1 in cells from estrogen-treated mice. Activated splenocytes from estrogen-treated mice had noticeably increased levels of the IFNγ-specific transcription factor T-bet, although there were no marked changes in phosphorylated STAT1. Estrogen-induced upregulation of T-bet was largely due to IFNγ 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.