Tumor necrosis factor-alpha induces substance P in sympathetic ganglia through sequential induction of interleukin-1 and leukemia inhibitory factor.
Tumor necrosis factor-alpha induces substance P in sympathetic ganglia through sequential induction of interleukin-1 and leukemia inhibitory factor.
复制标题
肿瘤坏死因子-α 通过依次诱导白介素-1 和白血病抑制因子，在交感神经节中诱导 P 物质。
DOI：
10.1002/neu.480280405
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Jonakait,GM
中科院分区：
文献类型：
--
作者：
Ding,M;Hart,RP;Jonakait,GM
本研究证实，肿瘤坏死因子-α诱导交感物质P(SP)需要白细胞介素1(IL-1)和白血病抑制因子(LIF)的序贯诱导。肿瘤坏死因子-α可剂量依赖性地诱导SP，这种诱导继发于SP前体蛋白原激肽原(PPT)基因的增加。由于肿瘤坏死因子-α条件培养液(CM)通过升高SP来模拟肿瘤坏死因子-α的作用，而这种作用不被中和的肿瘤坏死因子-α抗体所拮抗，因此肿瘤坏死因子-α诱导的SP是由一个或多个可溶中间体介导的。特异性IL-1受体拮抗剂阻断肿瘤坏死因子-α的作用和诱导IL-1m RNA的表达，提示IL-1是其中间产物之一。此外，由于LIF抗体的免疫沉淀降低了肿瘤坏死因子-αCM的SP诱导活性，而且由于LIF mRNA也是由肿瘤坏死因子-α诱导的，因此LIF是第二中间产物。此外，IL-1受体拮抗剂可阻断肿瘤坏死因子-α诱导的LIF mRNA，而IL-1诱导的LIF mRNA不受肿瘤坏死因子-α抗体的影响，提示肿瘤坏死因子-α首先诱导IL-1，IL-1随后诱导LIF。这些结果提示，肿瘤坏死因子-α通过诱导交感神经节产生SP。©1995 John Wiley&Sons，Inc.
The present study establishes that tumor necrosis factor‐α (TNF‐α) induction of sympathetic substance P (SP) requires sequential induction of both interleukin (IL‐1) and leukemia inhibitory factor (LIF). TNF‐α dose‐dependently induces SP, an induction that is secondory to an increase in the SP precursor, preprotachykinin (PPT), mRNA. Since TNF‐α conditioned medium (CM) mimics the effect of TNF‐α by raising SP, actions that are not antagonized by a neutralizing TNF‐α antibody, TNF‐α induction of SP is mediated by a soluble intermediate or intermediates. The blockade of TNF‐α action by a specific IL‐1 receptor antagonist and the induction of IL‐1 mRNA by TNF‐α suggest that IL‐1 is one of the intermediates. Moreover, because immunoprecipitation with LIF antibodies decreases SP‐inducing activity of TNF‐α CM, and because LIF mRNA is also induced by TNF‐α, LIF is a second intermediate. Furthermore, TNF‐α‐induced LIF mRNA is blocked by the IL1 receptor antagonist, whereas IL‐1‐induced LIF mRNA is not affected by TNF‐α antibodies, suggesting that TNF‐α first induces IL‐1, and IL‐1 subsequently induces LIF. These data suggest that TNF‐α induces SP in sympathetic ganglia through the sequential inductions of IL1 and LIF. © 1995 John Wiley & Sons, Inc.