Hattori A, Tanaka E, Murase K, Ishida N, Chatani Y, Tsujimoto M, Hayashi K, Kohno M
Department of Biology, Gifu Pharmaceutical University, Japan.
J Biol Chem. 1993 Feb 5;268(4):2577-82.
Tumor necrosis factor-alpha (TNF) markedly stimulates the synthesis and secretion of immunoreactive nerve growth factor (NGF) in quiescent mouse fibroblasts, which is a result of increase in the NGF mRNA level. NGF produced by TNF-treated fibroblasts has a molecular mass of 13 kDa on SDS-polyacrylamide gel electrophoresis, which is consistent in size with the subunit of mouse beta-NGF, and induces neurite outgrowth in paravertebral sympathetic neurons. Several peptide growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor also stimulate NGF production in the cells, but not platelet-derived growth factor. The dose responses of TNF and bFGF to stimulate NGF production in the cells are, respectively, similar to those to induce cell proliferation. However, no correlation is observed between the ability of these growth factors to stimulate NGF production and that to induce cell proliferation. Thus, the stimulation of NGF production in the cells seems to be a specific activity of TNF and some other growth factors. TNF stimulates the synthesis and secretion of NGF also in other cells such as human glioblastoma cells. These findings suggest that TNF plays a role in regulating neuronal cell function through an indirect mechanism by which it stimulates NGF production in glial cells and fibroblasts.
肿瘤坏死因子-α（TNF）可显著刺激静止的小鼠成纤维细胞合成和分泌免疫反应性神经生长因子（NGF），这是NGF mRNA水平升高的结果。经TNF处理的成纤维细胞产生的NGF在SDS-聚丙烯酰胺凝胶电泳上的分子量为13 kDa，其大小与小鼠β-NGF的亚基一致，并可诱导椎旁交感神经元的神经突生长。几种肽生长因子，如碱性成纤维细胞生长因子（bFGF）和表皮生长因子，也可刺激细胞中NGF的产生，但血小板衍生生长因子则不能。TNF和bFGF刺激细胞中NGF产生的剂量反应分别与诱导细胞增殖的剂量反应相似。然而，这些生长因子刺激NGF产生的能力与诱导细胞增殖的能力之间没有相关性。因此，刺激细胞中NGF的产生似乎是TNF和其他一些生长因子的特定活性。TNF也可刺激其他细胞如人胶质母细胞瘤细胞中NGF的合成和分泌。这些发现表明，TNF通过一种间接机制在调节神经元细胞功能中发挥作用，即它刺激神经胶质细胞和成纤维细胞中NGF的产生。
