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细胞因子诱导人胸膜细胞释放纤溶酶原激活物抑制剂-1的研究

Cytokine-induced release of plasminogen activator inhibitor-1 by human pleural mesothelial cells

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【作者】 闵锐李淑云王虹张劲松王彤杨玉

【Author】 MIN Rui, LI Shuyun,WANG Hong,et al. Department of Pulmonology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,China

【机构】 南京医科大学第一附属医院呼吸内科

【摘要】 目的 研究细胞因子对人胸膜间皮细胞 (HPMC)释放纤溶酶原激活物抑制剂 (PAI 1)的诱导效应。方法 取材于渗出性胸膜腔积液的 6份原代HPMC ,置于DMEM/F12培养液中体外孵育 ,观察白细胞介素 (IL) 1β、肿瘤坏死因子α(TNFα)和转化生长因子 (TGF) β1对HPMC纤溶活动的影响。对分离细胞的纯度进行光镜下细胞学形态、电镜下超微结构和免疫组化染色的鉴定 ,加入IL 1β、TNFα及TGF β1诱导培养第三代HPMC 2 4h后 ,对HPMC培养液中PAI 1活性采用底物显色法进行测定。结果 终浓度为 0 2 0、2 0 0和 2 0 0 0 μg/L水平的IL 1β、TNFα或TGF β1诱导培养第三代HPMC 2 4h后 ,均能显著增加HPMC培养液中的PAI 1活性 ,而且HPMC对TGF β1的反应显著高于对IL 1β或TNFα的反应。结论 炎症细胞因子在体内可能调节HPMC释放PAI 1,由此影响纤维蛋白在胸膜腔内的沉积而向纤维化发展。

【Abstract】 Objective To investigate the effects of inflammatory cytokines on the production of plasminogen activator inhibitor 1(PAI 1) by human pleural mesothelial cells (HPMC). Methods Six primary cultures of HPMC isolated from patients with exudative pleural effusion were incubated in DMEM/F12 medium to examine the effect of interleukin 1β(IL 1β), tumor necrosis factor α(TNFα) or transforming growth factor β1 (TGF β1) on the fibrinolytic properties of HPMC in vitro. The purity of the cell population was assessed by morphologic, ultrastructural and immunohistochemical characteristics. PAI 1 activity in the conditioned media of third passage HPMC was detected using chromogenic substrate method. Results As compared with the controls, PAI 1 activity in the conditioned media of HPMC increased significantly by stimulation with IL 1β,TNFα or TGF β1 for 24 hours at the level of 0 20 μg/L(IL 1β: q =3 38, P <0 05; TNFα: q =4 41, P <0 05;TGF β1: q =22 03, P <0 01), 2 00 μg/L(IL 1β: q =12 28, P <0 01; TNFα: q =16 60, P <0 01; TGF β1: q =19 23, P <0 01) and 20 00 μg/L(IL 1β: q =24 30, P <0 01; TNFα: q =25 00, P <0 01; TGF β1: q =49 30, P <0 01). Furthermore, HPMC responses to TGF β1 were significantly greater than those to IL 1β or TNFα. Conclusion These results suggest that inflammatory cytokines might mediate the release of PAI 1 by HPMC in vivo, affect the deposition of fibrin within the pleural cavity and favor fibrogenesis.

  • 【文献出处】 中华内科杂志 ,CHINESE JOURNAL OF INTERNAL MEDICINE , 编辑部邮箱 ,2000年09期
  • 【分类号】R655.2
  • 【被引频次】7
  • 【下载频次】70
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