von Boyen G B T, Steinkamp M, Reinshagen M, Schäfer K-H, Adler G, Kirsch J
Department of Medicine I (Gastroenterology), University of Ulm, Ulm, Germany.
J Neuroendocrinol. 2006 Nov;18(11):820-5. doi: 10.1111/j.1365-2826.2006.01478.x.
The enteric nervous system is composed of neurones and glial cells. These enteric glia cells (EGC) appear to be essential for the maintenance of gut homeostasis and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an important role for the gut integrity by regulating sensory and inflammatory processes in the intestines. Here, we demonstrate EGCs as one source of NGF and show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and lipopolysaccharides. NGF is continuously secreted from cultured EGCs and proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no effect on NGF expression. Furthermore, NGF secretion was sustained for more than 12 h after withdrawal of the proinflammatory cytokines, suggesting the involvement of transcriptional and/or translational processes. Thus, the release of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a higher expression of TrkA in EGCs. NGF, in turn, can increase visceral sensitivity and, on the other hand, appears to improve gut inflammation. Therefore, NGF secreting EGCs may play a key role in modulating visceral sensitivity and might be involved in inflammatory processes of the gut.
肠神经系统由神经元和神经胶质细胞组成。这些肠神经胶质细胞（EGC）似乎对维持肠道内环境稳定和黏膜完整性至关重要。神经营养因子神经生长因子（NGF）通过调节肠道中的感觉和炎症过程，对肠道完整性也起着重要作用。在此，我们证明EGC是NGF的一个来源，并显示在用促炎细胞因子和脂多糖刺激后，培养的EGC中NGF mRNA/蛋白和原肌球蛋白受体激酶A（TrkA）mRNA水平升高。NGF从培养的EGC中持续分泌，促炎细胞因子和脂多糖以时间和剂量依赖性方式刺激这种神经营养因子的分泌，而白细胞介素-4对NGF表达没有影响。此外，在撤除促炎细胞因子后，NGF分泌持续超过12小时，这表明涉及转录和/或翻译过程。因此，促炎细胞因子的释放可增加EGC分泌NGF，并导致EGC中TrkA表达升高。反过来，NGF可增加内脏敏感性，另一方面，似乎可改善肠道炎症。因此，分泌NGF的EGC可能在调节内脏敏感性中起关键作用，并可能参与肠道的炎症过程。
