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

Yamaguchi,Keisuke; Kumakura,Seiichiro; Murakami,Taisuke; Someya,Akimasa; Inada,Eiichi; Nagaoka,Isao

doi:10.3892/ijmm.2017.2875

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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Affiliations: Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan, Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
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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