Co-culture of monocytes and zona fasciculata adrenal cells: An in vitro model to study the immune-adrenal cross-talk.

Co-culture of monocytes and zona fasciculata adrenal cells: An in vitro model to study the immune-adrenal cross-talk.
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单核细胞和束状肾上腺细胞的共培养:研究免疫-肾上腺串扰的体外模型。

DOI:
10.1016/j.mce.2021.111195
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发表时间:
2021-04-15
影响因子:
4.1
通讯作者:
Spiga F
Spiga F
中科院分区:
医学2区
文献类型:
--
作者:
Fudulu DP;Horn G;Hazell G;Lefrançois-Martinez AM;Martinez A;Angelini GD;Lightman SL;Spiga F

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下丘脑-垂体-肾上腺轴是主要的神经内分泌系统,在应激期间(包括危重病和大手术)被激活以重建体内平衡。在危重病期间,有证据表明,局部诱导的肾上腺炎症可以促进免疫肾上腺串扰,进而调节皮质醇分泌。据推测,免疫细胞是必要的,以介导的影响,炎症刺激的类固醇生成途径,已在体内观察到。为了验证这一假设,我们开发并表征了THP 1(人单核细胞)衍生的巨噬细胞和ATC 7小鼠肾上腺皮质束状细胞的跨孔共培养模型。我们发现,ATC 7和THP 1细胞的共培养导致ATC 7细胞中IL-6 mRNA的基础水平显著增加,并且用LPS处理增强了这种效果。向ATC 7和THP 1的共培养物中添加LPS显著降低关键肾上腺类固醇生成酶(包括星星和DAX-1)的表达,并且这也在用促炎细胞因子处理的ATC 7细胞中发现。此外,用合成糖皮质激素地塞米松处理24小时可防止LPS刺激对与THP 1细胞共培养的ATC 7细胞中IL-6、星星和DAX-1 mRNA的影响。我们的数据表明,响应LPS的IL-6和类固醇基因的表达依赖于肾上腺内免疫细胞的激活。此外,我们还表明,脂多糖的影响可以调制糖皮质激素在一个时间和剂量依赖性的方式与临床实践的潜在影响。我们提出了一个肾上腺皮质细胞和单核细胞的共培养模型来研究免疫类固醇的串扰。LPS刺激共培养的ATC 7-THP 1细胞增加IL-6 mRNA并降低星星和DAX-1 mRNA表达。细胞因子对ATC 7-THP 1细胞和单独培养的ATC 7细胞中IL-6和类固醇生成基因mRNA的影响不同。DEX可剂量依赖性地抑制LPS诱导的ATC 7-THP 1细胞IL-6 mRNA表达和类固醇基因表达。ACTH诱导的肾上腺IL-6 mRNA表达和类固醇生成基因激活通过与THP 1细胞共培养来调节。
The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to re-establish homeostasis during periods of stress, including critical illness and major surgery. During critical illness, evidence suggests that locally induced inflammation of the adrenal gland could facilitate immune-adrenal cross-talk and, in turn, modulate cortisol secretion. It has been hypothesized that immune cells are necessary to mediate the effect of inflammatory stimuli on the steroidogenic pathway that has been observed in vivo. To test this hypothesis, we developed and characterized a trans-well co-culture model of THP1 (human monocytic cell)-derived macrophages and ATC7 murine zona fasciculata adrenocortical cells. We found that co-culture of ATC7 and THP1 cells results in a significant increase in the basal levels of IL-6 mRNA in ATC7 cells, and this effect was potentiated by treatment with LPS. Addition of LPS to co-cultures of ATC7 and THP1 significantly decreased the expression of key adrenal steroidogenic enzymes (including StAR and DAX-1), and this was also found in ATC7 cells treated with pro-inflammatory cytokines. Moreover, 24-h treatment with the synthetic glucocorticoid dexamethasone prevented the effects of LPS stimulation on IL-6, StAR and DAX-1 mRNA in ATC7 cells co-cultured with THP1 cells. Our data suggest that the expression of IL-6 and steroidogenic genes in response to LPS depends on the activation of intra-adrenal immune cells. Moreover, we also show that the effects of LPS can be modulated by glucocorticoids in a time- and dose-dependent manner with potential implications for clinical practice. We propose a co-culture model of adrenocortical cells and monocytes to investigate the immune-steroidogenic cross-talk. LPS stimulation of co-cultured ATC7-THP1 cells increases IL-6 mRNA and reduces StAR and DAX-1 mRNA expression. Cytokines effects on IL-6 and steroidogenic genes mRNA are different in co-cultured ATC7- THP1 cells and ATC7 cells alone. DEX prevents the LPS induced IL-6 mRNA expression and steroidogenic gene in ATC7-THP1 cells in a dose-dependent manner. ACTH induced adrenal IL-6 mRNA expression and steroidogenic genes activation are modulated by co-culture with THP1 cells.
DOI: 10.1056/nejmoa1214969
发表时间: 2013-04-18
期刊: The New England journal of medicine
影响因子: --
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Boonen E;Vervenne H;Meersseman P;Andrew R;Mortier L;Declercq PE;Vanwijngaerden YM;Spriet I;Wouters PJ;Vander Perre S;Langouche L;Vanhorebeek I;Walker BR;Van den Berghe G
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发表时间: 1992-03-01
期刊: ENDOCRINOLOGY
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影响因子: 20.1
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