Interleukin (IL)-6 and IL-8 production by human amnion: Regulation by cytokines, growth factors, glucocorticoids, phorbol esters, and bacterial lipopolysaccharide

Interleukin (IL)-6 and IL-8 production by human amnion: Regulation by cytokines, growth factors, glucocorticoids, phorbol esters, and bacterial lipopolysaccharide
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DOI:
10.1095/biolreprod57.6.1438
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发表时间:
1997-12-01
影响因子:
3.6
通讯作者:
Mitchell, MD
Mitchell, MD
中科院分区:
生物学2区
文献类型:
--
作者:
Keelan, JA;Sato, T;Mitchell, MD

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足月羊水中含有高浓度的白细胞介素 (IL)-6 和 IL-8。尽管胎膜(羊膜和绒毛膜)可能是这些细胞因子的来源,但这些细胞因子的来源尚未确定。通过使用酶消化分离的羊膜细胞(来自临产前足月分娩的胎盘)并在体外培养,研究了羊膜细胞因子的产生。通过 ELISA 测量条件培养基中的 IL-6 和 IL-8。在整个 7 天的培养期间,羊膜细胞产生了可检测量的 IL-6 和 IL-8。 IL-8 与 IL-6 的比例约为 5:1,与羊水中的比例相似。 IL-6和IL-8的产生以浓度依赖的方式受到白介素-1β(0.1-10ng/ml)、肿瘤坏死因子-α(1-100ng/ml)和细菌脂多糖(0.1-10μg/ml)以及100nM佛波醇12-肉豆蔻酸酯13-乙酸酯的刺激。表皮生长因子(1-25 ng/ml)对羊膜细胞因子的产生只有很小的影响。地塞米松 (10 nM) 在整个培养期间抑制 IL-6/-8 的产生约 50%。培养的羊膜成纤维细胞产生的IL-6/-8在基础条件下远低于上皮细胞,所有测试的试剂均以与上皮细胞相似的方式调节IL-6/-8。这些发现表明羊膜有助于羊水中的 IL-6 和 IL-8 库。我们推测,羊膜衍生的细胞因子在正常人类分娩过程中可能具有不同于其作为炎症介质的传统作用的功能。
Amniotic fluid at term contains high concentrations of interleukin (IL)-6 and IL-8. The source of these cytokines has not been identified, although the fetal membranes (amnion and chorion) are likely contributors. Amnion cytokine production was investigated by using amnion cells isolated by enzymatic digestion (from placentas delivered at term before labor) and cultured in vitro. IL-6 and IL-8 were measured in conditioned media by ELISA. Amnion cells produced detectable amounts of both IL-6 and IL-8 throughout the 7-day culture period. The ratio of IL-8 to IL-6 was approximately 5:1, similar to the ratio found in amniotic fluid. Production of both IL-6 and IL-8 was stimulated in a concentration-dependent fashion by interleukin-1 beta (0.1-10 ng/ml), tumor necrosis factor-alpha (1-100 ng/ml), and bacterial lipopolysaccharide (0.1-10 mu g/ml), and also by 100 nM phorbol 12-myristate 13-acetate. Epidermal growth factor (1-25 ng/ml) had only minimal effects on amnion cytokine production. Dexamethasone (10 nM) inhibited IL-6/-8 production by approximately 50% throughout the culture period. Production of IL-6/-8 by cultured amniotic fibroblasts, which under basal conditions was much lower than that by epithelial cells, was regulated by all the agents tested in a fashion similar to that of the epithelial cells. These findings suggest that the amnion contributes to the pool of IL-6 and IL-8 in amniotic fluid. We speculate that amnion-derived cytokines might have functions during normal human parturition that are distinct from their conventional roles as inflammatory mediators.