Interleukin-1 beta stimulates nitrite production in the rat ovary: evidence for heterologous cell-cell interaction and for insulin-mediated regulation of the inducible isoform of nitric oxide synthase.
Interleukin-1 beta stimulates nitrite production in the rat ovary: evidence for heterologous cell-cell interaction and for insulin-mediated regulation of the inducible isoform of nitric oxide synthase.
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Interleukin-1 beta 刺激大鼠卵巢中亚硝酸盐的产生：异源细胞间相互作用和胰岛素介导的一氧化氮合酶诱导亚型调节的证据。
DOI：
10.1095/biolreprod51.2.310
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发表时间：
1994
影响因子：
3.6
通讯作者：
Payne,DW
中科院分区：
文献类型：
--
作者：
Ben-Shlomo,I;Kokia,E;Jackson,MJ;Adashi,EY;Payne,DW
最近的研究表明，内源性产生的一氧化氮（NO）可能介导细胞因子在多种组织中的作用。为了确定NO的产生是否介导白细胞介素-1 β（IL-1 β）的任何卵巢内作用，我们观察并表征了IL-1 β处理的培养的全卵巢分散液中亚硝酸盐的积累。应用IL-1 β显著增加基础亚硝酸盐的释放，并呈剂量、细胞密度和时间依赖性，后者的特征为约20 h的滞后时间，提示NO合成酶（NOS）的诱导。IL-1 β还可提高细胞NOS活性。持续的亚硝酸盐积累需要持续应用IL-1 β。最大刺激剂量的IL-1 β（50 ng/ml）在培养96 h时使亚硝酸盐积累增加10倍，当细胞在底物中培养时（即，精氨酸）-无培养基。通过同时应用IL-1 β受体拮抗剂，IL-1 β刺激的亚硝酸盐积累降低至对照水平，从而表明特异性受体介导的效应。有利于诱导型NOS的抑制剂以剂量依赖性方式减弱了对照和IL-1 β刺激的亚硝酸盐积累水平。相比之下，NOS组成型的选择性抑制剂的效力明显较低。应用无活性的立体异构类似物后未观察到抑制作用。IL-1 β诱导的亚硝酸盐积累需要颗粒细胞和卵泡膜间质细胞之间的细胞-细胞相互作用。IL-1 β诱导的亚硝酸盐积累增加近2倍的胰岛素，虽然胰岛素单独没有影响。IL-1 β与已知调节卵巢功能的激素（胰岛素）的协同作用以及对颗粒细胞和卵泡膜间质细胞参与的要求表明NO可能在介导IL-1 β在卵巢中的某些多效性作用中发挥作用。这些研究表明，卵巢亚硝酸盐积累的依赖于精氨酸、IL-1 β诱导、受体介导、胰岛素增强的刺激，可能反映了NOS诱导型亚型的激活。
Recent studies suggest that endogenously generated nitric oxide (NO) may mediate the effects of cytokines in a variety of tissues. In an effort to determine whether NO generation mediates any of the intraovarian actions of interleukin-1 β (IL-1 β), we have looked for and characterized the accumulation of nitrite by IL-1 β-treated, cultured whole ovarian dispersates. Application of IL-1 β significantly enhanced basal nitrite release in a dose-, cell density- and time-dependent manner, the latter characterized by a lag time of about 20 h, suggestive of induction of NO synthase (NOS). Cellular NOS activity was also elevated by IL-1 β. Sustained nitrite accumulation required continuous application of IL-1 β. The maximally stimulating dose of IL-1 β (50 ng/ml) produced a 10-fold increase in nitrite accumulation by 96 h of culture, an effect reduced 23% when cells were cultured in substrate (i.e., arginine)-free media. IL-1 β-stimulated nitrite accumulation was reduced to control levels by the simultaneous application of an IL-1 β receptor antagonist, thereby suggesting a specific receptor-mediated effect. Both the control and IL-1 β-stimulated levels of nitrite accumulation were attenuated in a dose-dependent manner by inhibitors that favor the inducible form of NOS. In contrast, selective inhibitors of the constitutive form of NOS were significantly less potent. No inhibition was noted after application of an inactive stereoisomeric analogue. IL-1 β-induced nitrite accumulation was shown to require cell-cell interaction between granulosa and theca-interstitial cells. IL-1 β-induced nitrite accumulation was enhanced nearly 2-fold by the addition of insulin, although insulin alone had no effect. The synergy of IL-1 β with a hormone (insulin) known to regulate ovarian function as well as the requirement for participation of both granulosa and theca-interstitial cells suggests a possible role for NO in mediating some of the pleiotropic actions of IL-1 β in the ovary. These studies demonstrate an arginine-dependent, IL-1 β- induced, receptor-mediated, insulin-enhanced stimulation of ovarian nitrite accumulation, presumably reflecting activation of the inducible isoform of NOS.