Estrogen regulates cytokine production and apoptosis in PMA-differentiated, macrophage-like U937 cells
Estrogen regulates cytokine production and apoptosis in PMA-differentiated, macrophage-like U937 cells
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DOI：
10.1002/jcb.10607
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发表时间：
2003-09-01
影响因子：
4
通讯作者：
Cillari, E
中科院分区：
文献类型：
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作者：
Carruba, G;D'Agostino, P;Cillari, E
我们研究了性类固醇、雌二醇（E2）和睾酮（T）对佛波酯-肉豆蔻酸酯-乙酸酯（PMA）分化的人单核细胞U937细胞中肿瘤坏死因子α（TNF-α）和白细胞介素-10（IL-10）合成的影响。还检查了这两种激素调节巨噬细胞样PMA分化的U937细胞的活力和程序性细胞死亡的能力。E2增加TNF-α的合成，而T对这种细胞因子的产生没有影响。E2及其拮抗剂tamoxifen或ICI-182，789的组合完全消除了TNF-α的诱导，而T及其拮抗剂Casodex（CSDX）的组合并不显著影响U937细胞的TNF-α产生。细胞暴露于E2导致IL-10合成的剂量依赖性降低，而T再次未显示出任何可检测的作用。此外，E2诱导巨噬细胞样U937细胞凋亡的显着增加，这种增加被同时加入他莫昔芬或ICI-182抑制。与此相反，T单独或与CSDX组合并没有改变U937细胞的凋亡率。这些证据共同表明，雌激素而不是雄激素通过调节TNF-α和IL-10发挥促炎作用，并通过诱导程序性细胞死亡来调节免疫效应细胞。
We have investigated the effects of sex steroids, estradiol (E2), and testosterone (T) on the synthesis of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) in phorbol-myristate-acetate (PMA)-differentiated human monoblastic U937 cells. The ability of both hormones to modulate the viability and programmed cell death of macrophage-like PMA-differentiated U937 cells was also inspected. E2 increased TNF-alpha synthesis, whereas T had no effect on the production of this cytokine. The combination of E2 and its antagonist tamoxifen or ICI-182,789 completely abolished the induction of TNF-alpha, while combination of T and its antagonist Casodex (CSDX) did not significantly affect TNF-alpha production by U937 cells. Exposure of cells to E2 resulted in a dose-dependent decrease of IL-10 synthesis, while again T did not show any detectable effect. In addition, E2 induced a significant increase of apoptosis in macrophage-like U937 cells and this increase was inhibited by the simultaneous addition of either tamoxifen or ICI-182. In contrast, T alone or in combination with CSDX did not modify apoptotic rates of U937 cells. This evidence, taken together, suggests that estrogens, but not androgens, exert a pro-inflammatory action through the modulation of TNF-alpha and IL-10, and regulate the immune effector cells by the induction of programmed cell death.