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Eur J Immunol. 2010 Sep;40(9):2549-56. doi: 10.1002/eji.201040303.

Estrogen increases, whereas IL-27 and IFN-gamma decrease, splenocyte IL-17 production in WT mice.

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  • 1Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060-0342, USA.

Abstract

Estrogen-mediated regulation of Th1, Th2 and Treg effector functions are well documented but, surprisingly, there is little information whether estrogen modulates IL-17, a powerful proinflammatory cytokine that plays a pivotal role in several inflammatory and autoimmune diseases. Therefore in the current study, we determined whether estrogen regulates the expression levels of IL-17 in WT C57BL/6 mice. By ELISA, ELISPOT and/or flow cytometric analyses, we found that estrogen upregulated the levels of not only IL-17, but also the IL-17-specific transcription factor retinoic acid-related orphan receptor gamma t (ROR gamma t), in activated splenocytes. IL-17 levels were further enhanced by exposure of activated splenocytes to IL-23, particularly in cells from estrogen-treated mice. Exposure of splenocytes to IL-27 or IFN-gamma at the time of activation markedly inhibited the levels of IL-17 and ROR gamma t. Interestingly, a delay of 24 h in exposure of activated splenocytes to IL-27 or IFN-gamma decreased IL-17 levels (albeit less profoundly) but not ROR gamma t. These findings imply that the suppressive effects of IL-27 and IFN-gamma are more effective prior to the differentiation and commitment of IL-17-secreting cells. Furthermore, inhibition of JAK-2 by AG490 suppressed IL-17 but not ROR gamma t expression, suggesting that other transcription factors are also critical in estrogen-mediated upregulation of IL-17.

PMID:
20623549
[PubMed - indexed for MEDLINE]
PMCID:
PMC3097107
Free PMC Article

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