title: Dexmedetomidine suppresses interleukin-1β-induced interleukin-6 synthesis in rat glial cells.
abstract: Dexmedetomidine, an α2-adrenoceptor agonist, is used as a sedative medication for criticalyl ill patients and is known to exert neuroprotective effects by direct action on neurons and indirect action on neurons through astrocytes. Interleukin (IL)-6 plays a key role in neuroinflammation, which accompanies infection, traumatic brain injury, ischemia, neurodegenerative disorders, as both a pro-inflammatory cytokine and an anti-inflammatory cytokine. Dexmedetomidine suppresses immune function. However, the effects of dexmedetomidine on cytokine synthesis in the central nervous system (CNS) remain elusive. We previously reported that IL-1β stimulates IL-6 synthesis in the rat C6 glioma cell line through the phosphorylation of p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and IκB. In the present study, we investigated the effects of dexmedetomidine on the IL-1β-induced IL-6 synthesis in C6 cells. Dexmedetomidine inhibited the IL-1β-stimulated IL-6 release and mRNA expression in C6 cells. 8-Bromo-adenosine-3',5'-cyclic monophosphate, but not 8-bromo-guanosine 3',5'-cyclic monophosphate, significantly enhanced the IL-1β-induced IL-6 release and mRNA expression. However, dexmedetomidine failed to affect cAMP accumulation in the cells treated with IL-1β or forskolin, an activator of adenylyl cyclase. Yohimbine, an α2-adrenoceptor antagonist, did not reverse the suppressive effects of dexmedetomidine on the IL-1β-induced IL-6 release. Dexmedetomidine did not affect the IL-1β-induced phosphorylation of p38 MAP kinase, SAPK/JNK, IκB, nuclear factor (NF)-κB or c-Jun. Our findings strongly suggest that dexmedetomidine inhibits the IL-1β-induced IL-6 synthesis independently of the adenylyl cyclase-cAMP pathway through α2-adrenoceptors in C6 glioma cells. It is possible that dexmedetomidine may affect the immune system in the CNS by regulating the production of IL-6.
authors: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors: Kumiko
authors: K
authors: Tanabe
authors: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors: Rie
authors: R
authors: Matsushima-Nishiwaki
authors: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors: Osamu
authors: O
authors: Kozawa
authors: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors: Hiroki
authors: H
authors: Iida
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D020927:Dexmedetomidine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015016:Yohimbine; D020927:Dexmedetomidine; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate