Regulation of Sertoli cell IL-1 and IL-6 production in vitro

Regulation of Sertoli cell IL-1 and IL-6 production in vitro
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DOI:
10.1016/s0303-7207(97)00172-x
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发表时间:
1997-11-15
影响因子:
4.1
通讯作者:
Jegou, B
Jegou, B
中科院分区:
医学2区
文献类型:
--
作者:
Stephan, JP;Syed, V;Jegou, B

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白细胞介素-1(IL-1)和IL-6是由多种细胞类型产生的多效性细胞因子。在睾丸中,Sertoli细胞产生IL-1 α和IL-6。先前的研究已经证明,在体外,支持细胞IL-1 α的产生是由巨噬细胞IL-1的一些诱导剂刺激的,以及通过吞噬残余体。此外,我们还表明IL-1cr能够通过自分泌作用增强支持细胞IL-6的产生。本研究的目的是进一步研究支持细胞产生IL-1和IL-6的调控。测试了三类潜在调节剂:脂多糖(LPS)和酵母提取物酵母聚糖;促卵泡激素(FSH)、睾酮和地塞米松;肿瘤坏死因子α(TNF α)、干扰素γ(IFN γ)和神经生长因子β(NGF β)。发现酵母多糖(400-800 μ g/ml)和LPS(20 μ g/ml)刺激Sertoli细胞产生IL-1和IL-6。FSH(1 × 10(-2)-1 μ g/ml)和NGF(25-200 μ g/ml)以剂量依赖方式刺激Sertoli细胞IL-6水平,但对IL-1无影响。睾酮对Sertoli细胞IL-1和IL-6分泌的影响是双相的:低浓度(0.01-1 nM)时分泌显著增加,而较高浓度(100 nM)时无影响。地塞米松以浓度响应方式减少LPS诱导的IL-1和IL-6产生(分别为0.04-0.4和0.4-40 ng/ml)。向Sertoli细胞中添加TNF α导致两种细胞因子的剂量依赖性增加(IL-1为50-100 U/ml,IL-6为100-200 U/ml)。在IFN γ的情况下,中等浓度(50-100 U/ml)刺激IL-1 α,而最高浓度(200-400 U/ml)抑制IL-6。可以得出结论,支持细胞IL-1和IL-6的调节是非常复杂的,因为它涉及不同的因素,如激素,旁分泌因子和巨噬细胞的激活剂。后者可能是模仿病原体的作用或睾丸内药物的作用,其性质仍有待阐明。(C)1997 Elsevier Science爱尔兰有限公司
Interleukin-1 (IL-1) and IL-6 are pleiotropic cytokines produced by a large variety of cell types. In the testis, Sertoli cells produce IL-1 alpha and IL-6. Previous studies have demonstrated that, in vitro, Sertoli cell IL-1 alpha production is stimulated by some inducers of macrophage IL-1, as well as by phagocytosis of residual bodies. Furthermore, we have also shown that IL-lcr is able to enhance Sertoli cell IL-6 production by an autocrine action. The aim of the present study was to further investigate the regulation of Sertoli cell IL-1 and IL-6 production. Three categories of potential regulators were tested; the lipopolysaccharide (LPS) and the yeast extract zymosan; follicle stimulating hormone (FSH), testosterone and dexamethasone; tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and the nerve growth factor beta (NGF beta). It was found that zymosan (400-800 mu g/ml) and LPS (20 mu g/ml) stimulated Sertoli cell IL-1 and IL-6 production. FSH (1 x 10(-2)-1 mu g/ml) and NGF (25-200 mu g/ml) stimulated Sertoli cell IL-6 levels in a dose-dependent manner but had no effect on IL-1. The effect of testosterone on Sertoli cell IL-1 and IL-6 secretion was biphasic: dramatic increased secretion with low concentrations (0.01-1 nM) and no effect with the higher concentration tested (100 nM). Dexamethasone reduced LPS-induced IL-1 and IL-6 production in a concentration-responsive manner (0.04-0.4 and 0.4-40 ng/ml, respectively). Addition of TNF alpha to Sertoli cells resulted in a dose-dependent increase of both cytokines (50-100 U/ml for IL-1, 100-200 U/ml for IL-6). In the case of IFN gamma, intermediate concentrations (50-100 U/ml) stimulated IL-1 alpha, whereas the highest concentrations (200-400 U/ml) inhibited IL-6. It is concluded that regulation of Sertoli cell IL-1 and IL-6 is very complex as it involves factors as different as hormones, paracrine factors and activators of macrophages. The latter agents may be mimicking the action of pathogens or the action of intratesticular agents whose nature remains to be elucidated. (C) 1997 Elsevier Science Ireland Ltd.