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: Kumiko Tanabe, Rie Matsushima-Nishiwaki, Osamu Kozawa, Hiroki Iida
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 34 Issue 4 Pg. 1032-8 (Oct 2014) ISSN: 1791-244X [Electronic] Greece
• PMID: 25069417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• RNA, Messenger
• Receptors, Adrenergic, alpha-2
• Colforsin
• 8-Bromo Cyclic Adenosine Monophosphate
• Yohimbine
• Dexmedetomidine
• I-kappa B Kinase
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Tetradecanoylphorbol Acetate

Topics

• 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
• Animals
• Cell Line, Tumor
• Colforsin (pharmacology)
• Dexmedetomidine (pharmacology)
• Gene Expression Regulation (drug effects)
• I-kappa B Kinase (metabolism)
• Interleukin-1beta (pharmacology)
• Interleukin-6 (biosynthesis, genetics, metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Neuroglia (drug effects, metabolism)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics, metabolism)
• Rats
• Receptors, Adrenergic, alpha-2 (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Yohimbine (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)