Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells

  • Authors:
    • Keisuke Yamaguchi
    • Seiichiro Kumakura
    • Taisuke Murakami
    • Akimasa Someya
    • Eiichi Inada
    • Isao Nagaoka
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  • Published online on: February 3, 2017     https://doi.org/10.3892/ijmm.2017.2875
  • Pages: 687-692
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Abstract

The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1 receptor (NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate (NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP. In the present study, we investigated the anti-inflammatory effects of ketamine on the SP-induced activation of a human astrocytoma cell line, U373MG, which expresses high levels of NK-1R. The results from our experiments indicated that ketamine suppressed the production of interleukin (IL)-6 and IL-8 by the U373MG cells. Furthermore, ketamine inhibited the SP-induced activation of extracellular signal‑regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). Taken together, these observations suggest that ketamine may suppress the SP-induced activation (IL-6 and IL-8 production) of U373MG cells by inhibiting the phosphorylation of signaling molecules (namely ERK1/2, p38 MAPK and NF-κB), thereby exerting anti‑inflammatory effects. Thus, ketamine may modulate SP-induced inflammatory responses by NK-1R‑expressing cells through the suppression of signaling molecules (such as ERK1/2, p38 MAPK and NF-κB).
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March-2017
Volume 39 Issue 3

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

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Spandidos Publications style
Yamaguchi K, Kumakura S, Murakami T, Someya A, Inada E and Nagaoka I: Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells. Int J Mol Med 39: 687-692, 2017.
APA
Yamaguchi, K., Kumakura, S., Murakami, T., Someya, A., Inada, E., & Nagaoka, I. (2017). Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells. International Journal of Molecular Medicine, 39, 687-692. https://doi.org/10.3892/ijmm.2017.2875
MLA
Yamaguchi, K., Kumakura, S., Murakami, T., Someya, A., Inada, E., Nagaoka, I."Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells". International Journal of Molecular Medicine 39.3 (2017): 687-692.
Chicago
Yamaguchi, K., Kumakura, S., Murakami, T., Someya, A., Inada, E., Nagaoka, I."Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells". International Journal of Molecular Medicine 39, no. 3 (2017): 687-692. https://doi.org/10.3892/ijmm.2017.2875