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Estrogen increases, whereas IL‐27 and IFN‐γ decrease, splenocyte IL‐17 production in WT mice
Author(s) -
Khan Deena,
Dai Rujuan,
Karpuzoglu Ebru,
Ahmed Sattar Ansar
Publication year - 2010
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201040303
Subject(s) - splenocyte , estrogen , biology , rar related orphan receptor gamma , endocrinology , cytokine , medicine , interferon gamma , estrogen receptor , downregulation and upregulation , interleukin 17 , immunology , foxp3 , immune system , biochemistry , cancer , breast cancer , gene
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 γ t (RORγt ) , 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‐γ at the time of activation markedly inhibited the levels of IL‐17 and RORγt. Interestingly, a delay of 24 h in exposure of activated splenocytes to IL‐27 or IFN‐γ decreased IL‐17 levels (albeit less profoundly) but not RORγt. These findings imply that the suppressive effects of IL‐27 and IFN‐γ 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 RORγt expression, suggesting that other transcription factors are also critical in estrogen‐mediated upregulation of IL‐17.