Tumor necrosis factor α increases antifibrinolytic activity of cultured human mesangial cells
Tumor necrosis factor α increases antifibrinolytic activity of cultured human mesangial cells
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肿瘤坏死因子α增加培养的人系膜细胞的抗纤维蛋白溶解活性
DOI：
10.1038/ki.1992.293
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发表时间：
1992
影响因子：
19.6
通讯作者：
E. Rondeau
中科院分区：
文献类型：
--
作者：
Q. Meulders;Ci;C. Adida;M. Peraldi;W. Schleuning;J. Sraer;E. Rondeau
肿瘤坏死因子α增强人肾小球系膜细胞抗纤溶活性肿瘤坏死因子α（TNFα）可能在肾小球疾病的发病机制中发挥重要作用。除了其促炎特性外，TNFα还与细胞生长和纤维蛋白溶解系统组分的合成相互作用。本研究观察了重组人肿瘤坏死因子α（TNFα）对培养的人肾小球系膜细胞合成组织型纤溶酶原激活物（t-PA）及其抑制剂（派-1）的影响。我们首先证明TNFα特异性结合一类高亲和力受体（Kd 5.10 - 11 M; 1500个受体/细胞）。TNFα对人肾小球系膜细胞具有抗有丝分裂作用，因为其以剂量依赖性方式降低DNA合成（通过3 H-胸苷掺入测定）。与对照组相比，100 ng/ml TNFα未增加胞浆LDH的释放和掺入的51 Cr，表明该单核因子对培养的人系膜细胞无细胞毒性。酶谱分析和反向纤维蛋白自显影揭示了一个120 kD的t-PA-派-1复合物和50 kD的派-1的游离形式在未刺激和TNF刺激的细胞的上清液中，派-1释放过量，游离t-PA没有观察到。TNFα（0 ~ 100 ng/ml）对t-PA合成无影响，但以时间和剂量依赖性方式促进派-1释放（孵育24 h后派-1合成增加97%）。放线菌酮消除了这种影响，这表明蛋白质的合成是必需的。北方印迹分析显示TNFα以时间依赖的方式增加派-1 mRNA的稳态水平，在2 h时作用最大。最后，与大鼠系膜细胞的报道相反，我们未能通过免疫放射分析、免疫细胞化学和使用特异性TNFα cDNA探针的北方印迹分析证明人系膜细胞自身产生TNFα。我们的结论是，TNFα对培养的人肾小球系膜细胞具有抗有丝分裂活性，并增强派-1的合成。TNFα是否在体内肾小球派-1沉积和纤维蛋白持续存在中起作用仍有待确定。
Tumor necrosis factor α increases antifibrinolytic activity of cultured human mesangial cells. Tumor necrosis factorα (TNFα) is likely to exert a major influence in the pathogenesis of glomerulopathies. Besides its proinflammatory properties, TNFα interacts with cell growth and synthesis of components of the fibrinolytic system. In this study, we report the effects of recombinant human TNFα on the synthesis of tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) by human mesangial cells in culture. We first demonstrate that TNFα binds specifically to a single class of high affinity receptors (K d 5.10 -11 M; 1500 receptors/cell). TNFα has an antimitogenic effect on human mesangial cells since it decreased DNA synthesis, measured by 3 H-thymidine incorporation, in a dose-dependent manner. Release of cytosolic LDH and incorporated 51 Cr was not increased by 100 ng/ml TNFα as compared with control, indicating that this monokine is not cytotoxic for cultured human mesangial cells. Zymographic analysis and reverse fibrin autography disclosed a 120 kD t-PA-PAI-1 complex and a 50 kD free form of PAI-1 in the supernatants of both unstimulated and TNF-stimulated cells; PAI-1 was released in excess and free t-PA was not observed. TNFα (0 to 100 ng/ml) had no effect on t-PA synthesis, but enhanced PAI-1 release in a time- and dose-dependent manner (97% increase of PAI-1 synthesis after a 24 hour incubation). This effect was abolished by cycloheximide, suggesting that protein synthesis was required. Northern blot analysis showed that TNFα increased the steady-state PAI-1 mRNA levels in a time-dependent manner, with a maximal effect at two hours. Finally, in contrast to what was reported for rat mesangial cells, we failed to demonstrate a production of TNFα in human mesangial cells themselves by immunoradiometric assay, immunocytochemistry and Northern blot analysis using a specific TNFα cDNA probe. We conclude that TNFα has an antimitogenic activity on human mesangial cells in culture and enhances the synthesis of PAI-1. Whether TNFα plays a role in glomerular PAI-1 deposition and persistency of fibrin in vivo remains to be determined.
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影响因子：
3.9
作者：
Pal, Nabanita;Kim, Taeyeon;Park, Jae-Seo;Cho, Eun-Bum
通讯作者：
Cho, Eun-Bum
体外人肾小球细胞：分离和表征。
影响因子：
0.9
作者：
Striker,GE;Killen,PD;Farin,FM
通讯作者：
Farin,FM
DOI：
10.1073/pnas.80.10.2956
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LOSKUTOFF, DJ;VANMOURIK, JA;LAWRENCE, D
通讯作者：
LAWRENCE, D
DOI：
10.1073/pnas.83.12.4533
发表时间：
1986-06-01
影响因子：
11.1
作者：
BEVILACQUA, MP;POBER, JS;GIMBRONE, MA
通讯作者：
GIMBRONE, MA
IL-2 对淋巴细胞肿瘤坏死因子受体的调节。
DOI：
--
发表时间：
1989
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Owen-Schaub,LB;Crump3rd,WL;Morin,GI;Grimm,EA
通讯作者：
Grimm,EA