Stéphan J P, Syed V, Jégou B
Groupe d'Etude de la Reproduction chez le Mâle, INSERM U-435, Université de Rennes I, Campus de Beaulieu, Bretagne, France.
Mol Cell Endocrinol. 1997 Nov 15;134(2):109-18. doi: 10.1016/s0303-7207(97)00172-x.
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-1alpha and IL-6. Previous studies have demonstrated that, in vitro, Sertoli cell IL-1alpha 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-1alpha 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 (TNFalpha), interferon gamma (IFNgamma) and the nerve growth factor beta (NGFbeta). It was found that zymosan (400-800 microg/ml) and LPS (20 microg/ml) stimulated Sertoli cell IL-1 and IL-6 production. FSH (1 x 10(-2)-1 microg/ml) and NGF (25-200 ug/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 TNFalpha 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 IFNgamma, intermediate concentrations (50-100 U/ml) stimulated IL-1alpha, 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.
白细胞介素-1（IL-1）和白细胞介素-6是由多种细胞类型产生的多效性细胞因子。在睾丸中，支持细胞产生IL-1α和IL-6。先前的研究表明，在体外，巨噬细胞IL-1的一些诱导剂以及残余小体的吞噬作用可刺激支持细胞产生IL-1α。此外，我们还表明IL-1α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IL-1和IL-6产生的调节机制。测试了三类潜在的调节剂；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（TNFα）、干扰素γ（IFNγ）和神经生长因子β（NGFβ）。结果发现，酵母聚糖（400 - 800微克/毫升）和LPS（20微克/毫升）刺激支持细胞IL-1和IL-6的产生。FSH（1×10⁻² - 1微克/毫升）和NGF（25 - 200微克/毫升）以剂量依赖性方式刺激支持细胞IL-6水平，但对IL-1无影响。睾酮对支持细胞IL-1和IL-6分泌的影响是双相的：低浓度（0.01 - 1纳摩尔）时分泌显著增加，而在测试的较高浓度（100纳摩尔）时无影响。地塞米松以浓度响应方式降低LPS诱导的IL-1和IL-6产生（分别为0.04 - 0.4和0.4 - 40纳克/毫升）。向支持细胞中添加TNFα导致两种细胞因子呈剂量依赖性增加（IL-1为50 - 100单位/毫升，IL-6为100 - 200单位/毫升）。就IFNγ而言，中等浓度（50 - 100单位/毫升）刺激IL-1α，而最高浓度（200 - 400单位/毫升）抑制IL-6。结论是，支持细胞IL-1和IL-6的调节非常复杂，因为它涉及激素、旁分泌因子和巨噬细胞激活剂等不同因素。后一类物质可能模拟病原体的作用或睾丸内物质的作用，其性质尚待阐明。
