Syed V, Stéphan J P, Gérard N, Legrand A, Parvinen M, Bardin C W, Jégou B
Groupe d'Etude de la Reproduction chez le Mâle (GERM)-INSERM U-435, Université de Rennes 1, France.
Endocrinology. 1995 Jul;136(7):3070-8. doi: 10.1210/endo.136.7.7789334.
Interleukin-1 (IL-1) and IL-6 are produced by Sertoli cells. As IL-1 stimulates IL-6 production in some tissues, the cascade of events that results in IL-6 secretion by Sertoli cells was studied. The addition of IL-1 alpha to Sertoli cells resulted in a time-dependent increase in IL-6 secretion. Incubation of Sertoli cells with two known stimulators of IL-1 production, lipopolysaccharide (LPS) and residual bodies, resulted in a significant increase in IL-1 release into the medium several hours before IL-6 release. That IL-1 is essential for IL-6 production from Sertoli cells was established by blocking the actions of LPS and residual bodies with an anti-IL-1 alpha antibody. An increase in the release of IL-1 before IL-6 was also observed in medium obtained from staged segments of intact seminiferous tubules; IL-1 reached a maximum level at stage VIII, when mature spermatozoa are released and residual bodies are formed and phagocytosed. The secretion of IL-6 was low during this stage and then increased progressively from stage IX onward, consistent with IL-1 stimulation of IL-6. The pathway of IL-1 alpha-induced release of IL-6 was studied in the presence of agents that influence arachidonic acid release and metabolism. IL-1 alpha was found to stimulate arachidonic acid release by Sertoli cells. Furthermore, a phospholipase A2 inhibitor, aristolochic acid, significantly decreased IL-1-, LPS-, and pyrularia pubera thionin-induced IL-6 secretion from Sertoli cells. Indomethacin, a specific inhibitor of the cyclooxygenase pathway, had no significant effect on basal, but enhanced IL-1- and LPS-stimulated IL-6 production. The involvement of arachidonic acid metabolites produced in the lipoxygenase pathway on the release of IL-6 was investigated indirectly, using nordihydroguaiaretic acid. This inhibitor reduced basal and IL-1 alpha- and LPS-stimulated IL-6 production. Ethacrynic acid, an inhibitor of peptido-leukotriene synthesis, also reduced basal IL-6 levels and blocked IL-1 alpha- as well as LPS-induced IL-6 secretion. It is concluded that IL-1 produced by Sertoli cells in response to LPS or residual bodies induces IL-6 through the lipoxygenase pathway.
白细胞介素 -1（IL -1）和IL -6由支持细胞产生。由于IL -1在某些组织中刺激IL -6的产生，因此研究了导致支持细胞分泌IL -6的一系列事件。向支持细胞中添加IL -1α导致IL -6分泌呈时间依赖性增加。用两种已知的IL -1产生刺激物脂多糖（LPS）和残余小体孵育支持细胞，导致在IL -6释放前数小时培养基中IL -1释放显著增加。通过用抗IL -1α抗体阻断LPS和残余小体的作用，证实了IL -1对支持细胞产生IL -6至关重要。在从完整生精小管的分期节段获得的培养基中也观察到IL -1在IL -6之前释放增加；IL -1在VIII期达到最高水平，此时成熟精子释放，残余小体形成并被吞噬。在此阶段IL -6分泌较低，然后从IX期开始逐渐增加，这与IL -1对IL -6的刺激一致。在存在影响花生四烯酸释放和代谢的试剂的情况下，研究了IL -1α诱导IL -6释放的途径。发现IL -1α刺激支持细胞释放花生四烯酸。此外，磷脂酶A2抑制剂马兜铃酸显著降低支持细胞中IL -1、LPS和苦檀子素诱导的IL -6分泌。环氧化酶途径的特异性抑制剂吲哚美辛对基础分泌无显著影响，但增强了IL -1和LPS刺激的IL -6产生。使用去甲二氢愈创木酸间接研究了脂氧合酶途径中产生的花生四烯酸代谢产物对IL -6释放的影响。该抑制剂降低了基础以及IL -1α和LPS刺激的IL -6产生。依他尼酸是肽白三烯合成的抑制剂，也降低了基础IL -6水平并阻断了IL -1α以及LPS诱导的IL -6分泌。得出的结论是，支持细胞对LPS或残余小体作出反应产生的IL -1通过脂氧合酶途径诱导IL -6。
