DIFFERENTIAL REGULATION OF INTERLEUKIN-6 EXPRESSION IN HUMAN FIBROBLASTS BY TUMOR-NECROSIS-FACTOR-ALPHA AND LYMPHOTOXIN (Retracted Article)
DIFFERENTIAL REGULATION OF INTERLEUKIN-6 EXPRESSION IN HUMAN FIBROBLASTS BY TUMOR-NECROSIS-FACTOR-ALPHA AND LYMPHOTOXIN (Retracted Article)
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DOI：
10.1016/0014-5793(90)81256-n
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发表时间：
1990-09-17
期刊：
影响因子：
3.5
通讯作者：
HERRMANN, F
中科院分区：
文献类型：
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作者：
MANTOVANI, L;HENSCHLER, R;HERRMANN, F
用肿瘤坏死因子（TNP）-α和光敏素（LT）处理人二倍体成纤维细胞与诱导白细胞介素-6（IL-6）转录有关，TNF-α的效力是LT的10倍。在这里，我们报告了TNF-α/LT诱导的信号传导机制，负责调节这些细胞中IL-6基因的表达。连续试验表明，TNF-α和LT均通过该基因的转录激活增加IL-6 mRNA水平。成纤维细胞中IL-6转录物的稳定性研究表明，TNF-α延迟了IL-6 mRNA的衰减，但不延迟LT。异喹啉磺酰胺衍生物H7不抑制TNF-α和LT对IL-6转录物的诱导。类似地，12-O-十四烷酰基-佛波醇13-乙酸酯（TPA）对蛋白激酶C（PKC）的消耗并没有改变TNF-α和LT诱导IL-6转录的能力，表明这些药物的刺激可能不是通过激活PKC介导的。刺激成纤维细胞中的IL-6转录物也不需要新的蛋白质合成，因为在存在或不存在TNF-α或LT的情况下，暴露于蛋白质合成抑制剂放线菌酮（CHX）可增强IL-6 mRNA的蓄积。
The treatment of human diploid fibroblasts with tumor necrosis factor (TNP)‐α and with lymphotoxin (LT) is associated with induction of interleuk‐in‐6 (IL‐6) transcripts with TNF‐α being 10‐fold more potent than LT. Here we report on the TNF‐α/LT‐induced signaling mechanisms responsible for the regulation of IL‐6 gene expression in these cells. Run‐on assays demonstrated that both TNF‐α and LT increase IL‐6 mRNA levels by transcriptional activation of this gene. Stability studies of IL‐6 transcripts in fibroblasts showed that TNF‐α delayed IL‐6 mRNA decay but not LT. The induction of IL‐6 transcripts by TNF‐α and LT was not inhibited by the isoquinoline sulfonamide derivative H7. Similarly, depletion of protein kinase C (PKC) by 12‐O‐tetradecanoyl‐phorbol 13‐acetate (TPA) did not change the ability of TNF‐α and LT to induce IL‐6 transcripts, demonstrating that stimulation by these agents may not be mediated by activation of PKC. Stimulation of IL‐6 transcripts in fibroblasts did also not require new protein synthesis as exposure to the protein synthesis inhibitor cycloheximide (CHX) enhanced accumulation of IL‐6 mRNA in the presence or absence of TNF‐α or LT.