Estrogen receptor-α deficiency promotes increased TNF-α secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro
Estrogen receptor-α deficiency promotes increased TNF-α secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro
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DOI：
10.1189/jlb.1103589
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发表时间：
2004-06-01
影响因子：
5.5
通讯作者：
Estes, DM
中科院分区：
文献类型：
--
作者：
Lambert, KC;Curran, EM;Estes, DM
在这一系列研究中，我们确定了细胞内雌激素受体（ER） erα和erβ在巨噬细胞响应细菌刺激功能中的潜在作用。性激素17 -雌二醇（E-2）和内质网已被证明可以调节炎症反应以及辅助性T细胞1型(TH1)/TH2反应。E2及其受体用来改变这些免疫功能的机制在很大程度上仍然未知。erα和erβ在它们表达的组织中具有复杂的作用。我们描述了小鼠树突状细胞和巯基乙酸酯诱导的腹膜巨噬细胞（PM）的受体库。两种细胞类型都表达erα的mRNA。两种细胞类型均表达可检测量的ERbeta mRNA，通过使用跨越七个内含子/外显子连接处的外显子特异性引物的逆转录聚合酶链反应确定。来自erα -和erβ -缺陷严重联合免疫缺陷小鼠的原代巨噬细胞[分别是erα敲除（KO）和ERbetaKO]被用来描述类固醇受体调节巨噬细胞功能的作用和潜在机制。与野生型（WT） PM相比，体外暴露于脂多糖或鸟分枝杆菌的erα缺陷PM显示出肿瘤坏死因子α (tnf - α)分泌的显著增加以及细菌负荷的减少。相比之下，erβ缺乏的PM在tnf - α分泌或细菌负荷方面与WT幼崽没有显著差异。这些研究表明，erα，而不是erβ，调节小鼠的PM功能。
In this series of studies, we determined the potential role of intracellular estrogen receptors (ER), ERalpha and ERbeta, on macrophage function in response to bacterial stimuli. The sex hormone 17beta-estradiol (E-2) and ER have been shown to modulate inflammatory responses as well as T helper cell type 1 (TH1)/TH2 responses. The mechanisms E2 and its receptors use to alter these immune functions remain largely unknown. ERalpha and ERbeta possess complex actions in tissues where they are expressed. We have characterized the receptor repertoire of murine dendritic cells and thioglycollate-elicited peritoneal macrophages (PM). Both cell types express mRNA for ERalpha. Neither cell type expressed detectable amounts of ERbeta mRNA, as determined by reverse transcriptase-polymerase chain reaction using exon-specific primers spanning each of the seven intron/exon junctions. Primary macrophages from ERalpha- and ERbeta-deficient severe combined immunodeficiency mice [ERalpha-knockout (KO) and ERbetaKO, respectively] were used to delineate the effects and potential mechanisms via which steroid receptors modulate macrophage function. ERalpha-deficient PM exposed ex vivo to lipopolysaccharide or Mycobacterium avium exhibited significant increases in tumor necrosis factor alpha (TNF-alpha) secretion as well as reduction in bacterial load when compared with wild-type (WT) PM. In contrast, ERbeta-deficient PM possessed no significant difference in TNF-alpha secretion or in bacterial load when compared with WT littermates. These studies suggest that ERalpha, but not ERbeta, modulates murine PM function.