Cao Zixuan, Gao Ying, Bryson J Barney, Hou Jianwei, Chaudhry Nagarathnamma, Siddiq Mustafa, Martinez Jennifer, Spencer Tim, Carmel Jason, Hart Ronald B, Filbin Marie T
Department of Biological Sciences, Hunter College, The City University of New York, New York, New York 10021, USA.
J Neurosci. 2006 May 17;26(20):5565-73. doi: 10.1523/JNEUROSCI.0815-06.2006.
Lesioning the peripheral branch of a dorsal root ganglion (DRG) neuron before injury of the central branch of the same neuron enables spontaneous regeneration of these spinal axons. This effect is cAMP and transcription dependent. Here, we show that the cytokine interleukin-6 (IL-6) is upregulated in DRG neurons after either a conditioning lesion or treatment with dibutyryl-cAMP. In culture, IL-6 allows neurons to grow in the presence of inhibitors of regeneration present in myelin. Importantly, intrathecal delivery of IL-6 to DRG neurons blocks inhibition by myelin both in vitro and in vivo, effectively mimicking the conditioning lesion. Blocking IL-6 signaling has no effect on the ability of cAMP to overcome myelin inhibitors. Consistent with this, IL-6-deficient mice respond to a conditioning lesion as effectively as wild-type mice. We conclude that IL-6 can mimic both the cAMP effect and the conditioning lesion effect but is not an essential component of either response.
在背根神经节（DRG）神经元的中枢支损伤之前，对其外周支进行损伤，可使这些脊髓轴突自发再生。这种效应依赖于环磷酸腺苷（cAMP）和转录。在此，我们表明，无论是进行预处理损伤还是用二丁酰环磷腺苷（dibutyryl-cAMP）处理后，DRG神经元中的细胞因子白细胞介素-6（IL-6）都会上调。在培养过程中，IL-6可使神经元在髓鞘中存在的再生抑制剂的情况下生长。重要的是，向DRG神经元鞘内注射IL-6，在体外和体内均可阻断髓鞘的抑制作用，有效地模拟了预处理损伤。阻断IL-6信号传导对cAMP克服髓鞘抑制剂的能力没有影响。与此一致的是，IL-6基因缺陷小鼠对预处理损伤的反应与野生型小鼠一样有效。我们得出结论，IL-6可以模拟cAMP效应和预处理损伤效应，但不是这两种反应的必需成分。
