Estrogen selectively regulates chemokines in murine splenocytes
Estrogen selectively regulates chemokines in murine splenocytes
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DOI：
10.1189/jlb.0606391
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Ahmed, S. Ansar
中科院分区：
文献类型：
--
作者：
Lengi, Andrea J.;Phillips, Rebecca A.;Ahmed, S. Ansar
雌激素对免疫和炎症性自身免疫性疾病具有显着的影响。雌激素诱导的免疫调节和炎性自身免疫性疾病的一个潜在机制是通过改变淋巴细胞分泌趋化因子，这方面迄今没有得到很好的解决。我们发现雌激素对活化的脾细胞分泌趋化因子有显著的，但不同的影响。与安慰剂处理的对照组相比，雌激素处理显著增加了Con A激活的脾细胞MCP-1、MCP-5、嗜酸性粒细胞趋化因子和基质细胞衍生因子1 β的分泌，并且在24 h时对RANTES、胸腺和激活调节趋化因子以及角质形成细胞衍生趋化因子（KC）的水平没有影响。动力学分析表明，随着刺激时间的延长，趋化因子呈增加趋势，但只有MCP-1和MCP-5在雌激素处理的小鼠脾细胞中表现出增加的生物学趋势，而KC在雌激素处理的脾细胞中在18 h时显著降低。雌激素不影响24 h时趋化因子受体CCR 1和CCR 2的蛋白水平。雌激素诱导的MCP-1和MCP-5水平的改变部分地由IFN-γ介导，因为与野生型小鼠不同，IFN-γ缺失小鼠的雌激素治疗没有上调这些趋化因子。然而，添加重组IFN-γ导致MCP-1和MCP-5的分泌仅在来自雌激素处理的小鼠的细胞中显著增加。这些研究提供了新的数据，表明雌激素可能通过改变趋化因子的水平来促进炎症，为雌激素调节炎症的另一种机制提供了证据。
Estrogen has striking effects on immunity and inflammatory autoimmune conditions. One potential mechanism of estrogen-induced regulation of immunity and inflammatory autoimmune conditions is by altering the secretion of chemokines by lymphocytes, an aspect not well addressed thus far. We found that estrogen has marked, but differential, effects on the secretion of chemokines from activated splenocytes. Estrogen treatment significantly increased the secretion of MCP-1, MCP-5, eotaxin, and stromal cell-derived factor 1 beta from Con A-activated splenocytes when compared with placebo-treated controls, and it had no effects on the levels of RANTES, thymus and activation-regulated chemokine, and keratinocyte-derived chemokine (KC) at 24 h. A kinetic analysis showed that chemokines tended to increase with stimulation time, but only MCP-1 and MCP-5 showed a biological trend of increasing in splenocytes from estrogen-treated mice, and KC was decreased significantly in estrogen-treated splenocytes at 18 h. Estrogen did not affect the protein levels of chemokine receptors CCR1 or CCR2 at 24 h. Estrogen-induced alterations in the levels of MCP-1 and MCP-5 are mediated, in part, by IFN-gamma, as estrogen treatment of IFN-gamma null mice, unlike wild-type mice, did not up-regulate these chemokines. However, addition of recombinant IFN-gamma resulted in markedly increased secretion of MCP-1 and MCP-5 only in the cells derived from estrogen-treated mice. These studies provide novel data indicating that estrogen may promote inflammatory conditions by altering the levels of chemokines, providing evidence for an additional mechanism by which estrogens can regulate inflammation.