TNF induces c‐fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite.
TNF induces c‐fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite.
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TNF 通过一种需要将花生四烯酸转化为脂氧合酶代谢物的新途径诱导 c-fos。
DOI：
10.1002/j.1460-2075.1991.tb07926.x
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
G. Ringold
中科院分区：
文献类型：
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作者：
E. Haliday;C. Ramesha;G. Ringold
肿瘤坏死因子（TNF）是一种由活化的巨噬细胞释放的淋巴因子，对多种细胞类型具有不同的作用。TNF通过特定的细胞表面受体发挥这些作用;然而，对随之发生的生化事件知之甚少。我们已经证明，TNF在成脂性TA 1细胞系中快速诱导原癌基因c-fos和c-jun，并使用这些反应来表征TNF作用的细胞内介质。我们发现，响应TNF释放的花生四烯酸在静止的TA 1细胞中诱导c-fos而不是c-jun mRNA。用脂氧合酶抑制剂预处理细胞可以消除TNF对c-fos的诱导作用，而对c-jun的诱导作用不受影响;相反，环氧合酶抑制剂对这两种反应都没有影响。最后，我们已经证明，TNF刺激TA 1细胞中脂氧合酶代谢产物的产生，其中之一，5-HPETE，诱导c-fos，但不是c-jun。这些数据表明，TNF激活两个第二信使途径，其中之一是依赖于花生四烯酸的释放及其随后转化为脂氧合酶代谢产物。
Tumour necrosis factor (TNF), a lymphokine released by activated macrophages, has diverse effects on a wide variety of cell types. TNF exerts these effects via specific cell surface receptors; however little is known of the biochemical events that ensue. We have shown that TNF rapidly induces the proto‐oncogenes c‐fos and c‐jun in the adipogenic TA1 cell line and have used these responses to characterize the intracellular mediators of TNF action. We find that arachidonic acid, which is released in response to TNF, induces c‐fos, but not c‐jun mRNA in quiescent TA1 cells. Pretreatment of the cells with lipoxygenase inhibitors abolishes the induction of c‐fos by TNF, while the induction of c‐jun is unaffected; in contrast, a cyclooxygenase inhibitor has no effect on either response. Finally, we have demonstrated that TNF stimulates production of lipoxygenase metabolites in TA1 cells and that one of these, 5‐HPETE, induces c‐fos, but not c‐jun. These data suggest that TNF activates two second messenger pathways, one of which is dependent on release of arachidonic acid and its subsequent conversion to a lipoxygenase metabolite.