title: Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells.
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).
authors.affiliation: Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kumakura
authors.affiliation: Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Someya
authors.affiliation: Department of Anesthesiology and Pain Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Inada
authors.affiliation: Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
mesh_terms: D001254:Astrocytoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007649:Ketamine / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D013373:Substance P; D007649:Ketamine; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases