Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.
Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.
复制标题
细胞因子和内毒素刺激人肝细胞中的一氧化氮合酶途径。
DOI：
10.1084/jem.176.1.261
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发表时间：
1992-07-01
期刊：
影响因子：
--
通讯作者：
Simmons RL
中科院分区：
文献类型：
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作者：
Nussler AK;Di Silvio M;Billiar TR;Hoffman RA;Geller DA;Selby R;Madariaga J;Simmons RL
一氧化氮（NO）是一种短寿命的生物介质，其在各种细胞类型中被诱导并引起靶细胞中的许多代谢变化。抑制肿瘤细胞生长和抗微生物活性归因于诱导型NO合酶（NOS）的刺激。然而，在人类细胞类型中存在这种诱导型NOS的证据有限。在这里，我们显示了在新鲜分离的人肝细胞（HC）刺激后，与白细胞介素1，肿瘤坏死因子（TNF），IFN-γ，和内毒素的NO生物合成的诱导。培养上清液中亚硝酸盐（NO2-）和硝酸盐（NO3-）水平的增加与细胞裂解物中NADPH依赖性NOS活性有关。NO 2-和NO 3-的产生被NG-单甲基L-精氨酸抑制，并与环鸟苷酸单磷酸释放的增加有关。这里提供的数据提供了证据，在人类细胞类型中存在典型的诱导型NO生物合成。
Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced in various cell types and to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of the inducible type of the NO synthase (NOS). However, there is limited evidence for the existence of such inducible NOS in a human cell type. We show here the induction of NO biosynthesis in freshly isolated human hepatocytes (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN- gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in culture supernatants were associated with NADPH-dependent NOS activity in the cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L-arginine and was associated with an increase in cyclic guanylate monophosphate release. The data presented here provide evidence for the existence of typical inducible NO biosynthesis in a human cell type.