Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2.
Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2.
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DOI：
10.1016/s0021-9258(18)54804-3
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发表时间：
1991-11
期刊：
影响因子：
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通讯作者：
Sanjay Kumar;Corrado Baglioni
中科院分区：
文献类型：
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作者：
Sanjay Kumar;Corrado Baglioni
HT-1080纤维肉瘤细胞与肿瘤坏死因子（TNF）的预处理诱导抵抗这种细胞因子与放线菌酮结合的细胞溶解活性。这种耐药与纤溶酶原激活物抑制剂-2（派-2）的合成有关。用派-2表达载体以正义和反义方向转染HT-1080细胞。转染细胞克隆对TNF介导的细胞溶解的抗性与派-2表达水平相关。表达反义派-2 RNA的细胞表现出派-2表达减少和对TNF介导的细胞溶解的敏感性增加。用TNF和放线菌酮处理组成型表达派-2的细胞，以选择对细胞溶解的抗性增加和派-2表达增强的细胞。派-2在TNF和放线菌酮治疗期间逐渐消失。这一发现表明派-2与靶蛋白酶形成复合物，其可能参与介导TNF的细胞溶解活性。
Pretreatment of HT-1080 fibrosarcoma cells with tumor necrosis factor (TNF) induced resistance to the cytolytic activity of this cytokine in combination with cycloheximide. This resistance correlated with the synthesis of plasminogen activator inhibitor type-2 (PAI-2). HT-1080 cells were transfected with a PAI-2 expression vector in both sense and antisense orientation. The resistance to TNF-mediated cytolysis of transfected cell clones was correlated with the level of PAI-2 expression. Cells expressing antisense PAI-2 RNA showed reduced expression of PAI-2 and increased sensitivity to TNF-mediated cytolysis. Cells expressing constitutively PAI-2 were treated with TNF and cycloheximide to select cells with increased resistance to cytolysis and enhanced PAI-2 expression. PAI-2 gradually disappeared during a treatment with TNF and cycloheximide. This finding suggested that PAI-2 formed a complex with a target proteinase, which could be involved in mediating the cytolytic activity of TNF.