Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury

  • Authors:
    • Gang Yang
    • Wen-Yuan Tang
  • View Affiliations

  • Published online on: January 5, 2017     https://doi.org/10.3892/ijmm.2017.2848
  • Pages: 437-445
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Abstract

Interleukin-6 (IL)-6 was originally discovered as a factor that contributes to the secondary pathological and inflammatory response in the central nervous system (CNS) following injury. However, accumulating evidence suggests that IL-6 is also involved in functional and structural recovery following CNS injury by promoting axonal sprou­ting. This suggests a potential dual role of IL-6 in CNS injury. However, the definitive function of IL-6 in neural injury and the corresponding underlying mechanisms are still topics of controversy. The present study was carried out to examine the potential function of IL-6 in resistance to neurite growth‑inhibitory effects via regulation of the expression of growth associated protein-43 (GAP-43), myelin-associated neurite outgrowth inhibitor (Nogo-A) and its receptor (NgR). Rat dorsal root ganglion (DRG) neurons cultured in an inhibitory microenvironment mimicking injured CNS were used to investigate the effects of IL-6 on the outgrowth of neuronal processes. Additionally, IL-6 was subarachnoidally injected into rats to establish a spinal cord injury (SCI) model, and the neurobehavioral manifestations and neural morphology were subsequently evaluated to determine the effect of IL-6 on neural regeneration. Finally, the potential molecular mechanisms of IL-6-mediated rege­neration and functional recovery following CNS injury are discussed. The results of the present study demonstrated that the in vitro administration of IL-6 enhanced the neurite outgrowth of DRG neurons in a dose-dependent manner via resisting the inhibitory function of myelin proteins. All doses of the IL-6 subarachnoid injection improved the Basso, Beattie and Bresnahan scores following SCI, with a large number of axonal sproutings observed at the spinal lesion site, and several sprouting fibers being elongated and bypassing the lesion and entered the caudal spinal cord. Additionally, a significantly increased density area of diaminobenzidine-labeled neural fiber was observed in rats that received a subarachnoid injection of IL-6, and the rats exhibited increased expression of GAP-43 and decreased expression of Nogo-A. In conclusion, the results of the present study indicated that IL-6 interferes with the inhibitory functions of myelin proteins by upregulating the expression of GAP-43 and simultaneously downregulating the expression of Nogo-A and NgR to promote axonal sprouting and functional recovery following SCI.
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February-2017
Volume 39 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yang G and Yang G: Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury. Int J Mol Med 39: 437-445, 2017
APA
Yang, G., & Yang, G. (2017). Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury. International Journal of Molecular Medicine, 39, 437-445. https://doi.org/10.3892/ijmm.2017.2848
MLA
Yang, G., Tang, W."Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury". International Journal of Molecular Medicine 39.2 (2017): 437-445.
Chicago
Yang, G., Tang, W."Resistance of interleukin-6 to the extracellular inhibitory environment promotes axonal regeneration and functional recovery following spinal cord injury". International Journal of Molecular Medicine 39, no. 2 (2017): 437-445. https://doi.org/10.3892/ijmm.2017.2848