Ding M, Hart R P, Jonakait G M
Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA.
J Neurobiol. 1995 Dec;28(4):445-54. doi: 10.1002/neu.480280405.
The present study establishes that tumor necrosis factor-alpha (TNF-alpha) induction of sympathetic substance P (SP) requires sequential induction of both interleukin (IL-1) and leukemia inhibitory factor (LIF). TNF-alpha dose-dependently induces SP, an induction that is secondary to an increase in the SP precursor, preprotachykinin (PPT), mRNA. Since TNF-alpha conditioned medium (CM) mimics the effect of TNF-alpha by raising SP, actions that are not antagonized by a neutralizing TNF-alpha antibody, TNF-alpha induction of SP is mediated by a soluble intermediate or intermediates. The blockade of TNF-alpha action by a specific IL-1 receptor antagonist and the induction of IL-1 mRNA by TNF-alpha suggest that IL-1 is one of the intermediates. Moreover, because immunoprecipitation with LIF antibodies decreases SP-inducing activity of TNF-alpha CM, and because LIF mRNA is also induced by TNF-alpha, LIF is a second intermediate. Furthermore, TNF-alpha-induced LIF mRNA is blocked by the IL-1 receptor antagonist, whereas IL-1-induced LIF mRNA is not affected by TNF-alpha antibodies, suggesting that TNF-alpha first induces IL-1, and IL-1 subsequently induces LIF. These data suggest that TNF-alpha induces SP in sympathetic ganglia through the sequential inductions of IL-1 and LIF.
本研究证实，肿瘤坏死因子-α（TNF-α）诱导交感神经P物质（SP）需要先后诱导白细胞介素（IL-1）和白血病抑制因子（LIF）。TNF-α以剂量依赖方式诱导SP，这种诱导是由于SP前体、前速激肽原（PPT）mRNA增加所致。由于TNF-α条件培养基（CM）通过提高SP来模拟TNF-α的作用，且这些作用不受中和性TNF-α抗体的拮抗，因此TNF-α诱导SP是由一种或多种可溶性中间体介导的。特异性IL-1受体拮抗剂对TNF-α作用的阻断以及TNF-α对IL-1 mRNA的诱导表明IL-1是其中一种中间体。此外，由于用LIF抗体进行免疫沉淀会降低TNF-α CM的SP诱导活性，且LIF mRNA也由TNF-α诱导，所以LIF是第二种中间体。此外，TNF-α诱导的LIF mRNA被IL-1受体拮抗剂阻断，而IL-1诱导的LIF mRNA不受TNF-α抗体影响，这表明TNF-α首先诱导IL-1，随后IL-1诱导LIF。这些数据表明，TNF-α通过先后诱导IL-1和LIF在交感神经节中诱导SP。
