Estrogen increases, whereas IL-27 and IFN-gamma decrease, splenocyte IL-17 production in WT mice.
Estrogen increases, whereas IL-27 and IFN-gamma decrease, splenocyte IL-17 production in WT mice.
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DOI:
10.1002/eji.201040303
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发表时间:
2010-09
影响因子:
5.4
通讯作者:
Ahmed, Sattar Ansar
中科院分区:
文献类型:
--
作者:
Khan, Deena;Dai, Rujuan;Karpuzoglu, Ebru;Ahmed, Sattar Ansar
Estrogen-mediated regulation of Th1, Th2 and Treg effector functions are well documented but, surprisingly, it is still not known whether estrogen modulates IL-17, a powerful proinflammatory cytokine that plays a pivotal role in several inflammatory and autoimmune diseases. Therefore in the present study, we determined whether estrogen regulates the expression levels of IL-17 in wildtype 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 (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 hours 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.
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影响因子:
64.8
作者:
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者:
Kuchroo, VK
影响因子:
30.5
作者:
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
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Bonnefoy-Berard, Nathalie
影响因子:
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Lengi, Andrea J.;Phillips, Rebecca A.;Ahmed, S. Ansar
通讯作者:
Ahmed, S. Ansar
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4.4
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Diveu, Caroline;McGeachy, Mandy J.;Kastelein, Robert A.
通讯作者:
Kastelein, Robert A.
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作者:
Fitzgerald, Denise C.;Ciric, Bogoljub;Rostami, Abdolmohamad
通讯作者:
Rostami, Abdolmohamad