The neurosensory tachykinins substance P and neurokinin A directly induce keratinocyte nerve growth factor
The neurosensory tachykinins substance P and neurokinin A directly induce keratinocyte nerve growth factor
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DOI：
10.1046/j.0022-202x.2001.01498.x
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发表时间：
2001-11-01
影响因子：
6.5
通讯作者：
Armstrong, CA
中科院分区：
文献类型：
--
作者：
Burbach, GJ;Kim, KH;Armstrong, CA
神经生长因子是皮肤感觉神经生长和维持所必需的神经营养因子。在皮肤中，角质形成细胞是神经生长因子的重要来源;然而，皮肤神经生长因子产生的调节仍有待充分理解。在这项研究中，我们测试的假设，皮肤感觉神经释放的神经肽有能力直接调节角质形成细胞神经生长因子的表达，这将有重要的意义，在皮肤中的神经的维护和修复。为了解决这个问题，我们研究了实验的神经肽，P物质和神经激肽A，在人角质形成细胞和小鼠角质形成细胞PAM 212细胞系的神经生长因子表达的影响，通过定量逆转录酶-聚合酶链反应，酶联免疫吸附试验，和PC-12神经生长因子生物测定。这些研究结果表明，P物质和神经激肽A可以直接诱导人和小鼠角质形成细胞中神经生长因子mRNA的表达和生物活性神经生长因子蛋白的分泌。使用神经肽受体拮抗剂和神经生长因子阻断抗体证明了这些反应的特异性。另外的研究也证明了局部应用神经肽释放剂辣椒素后，小鼠表皮中角质细胞神经生长因子表达的体内显著上调。这是第一个报告证明皮肤神经生长因子的诱导感觉神经源性神经肽，如P物质和神经激肽A。神经感觉系统对角质形成细胞神经生长因子产生的这种直接作用可能对正常皮肤中以及炎症和伤口愈合期间的皮肤神经的维持和再生具有重要后果。
Nerve growth factor is an essential neurotrophic factor required for the growth and maintenance of cutaneous sensory nerves. In the skin, keratinocytes are a significant source of nerve growth factor; however, the regulation of cutaneous nerve growth factor production still remains to be fully understood. In this study we tested the hypothesis that neuropeptides released by cutaneous sensory nerves have the capacity to modulate directly the expression of keratinocyte nerve growth factor, which would have important implications for the maintenance and repair of nerves in the skin. In order to address this question experimentally we examined the effect of the neuropeptides, substance P and neurokinin A, on nerve growth factor expression in human keratinocytes and the murine keratinocyte PAM 212 cell line by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and the PC-12 nerve growth factor bioassay. The results of these studies indicated that substance P and neurokinin A can directly induce nerve growth factor mRNA expression and the secretion of bioactive nerve growth factor protein in both human and murine keratinocytes. The specificity of these responses was demonstrated using neuropeptide receptor antagonists and nerve growth factor blocking antibodies. Additional studies also demonstrated a significant in vivo upregulation of keratinocyte nerve growth factor expression in murine epidermis after the topical application of the neuropeptide releasing agent capsaicin. This is the first report demonstrating the induction of cutaneous nerve growth factor by sensory nerve-derived neuropeptides such as substance P and neurokinin A. This direct effect of the neurosensory system on keratinocyte nerve growth factor production may have important consequences for the maintenance and regeneration of cutaneous nerves in normal skin and during inflammation and wound healing.