Adenylyl Cyclase 6 Mediates Inhibition of TNF in the Inflammatory Reflex
| Autor: | Jianhua Li, Laura Tarnawski, Mauricio Rosas-Ballina, Yaakov A. Levine, Michael W. Tusche, Sangeeta S. Chavan, April S. Caravaca, Valentin A. Pavlov, La Queta K. Hudson, Kaie Ojamaa, Colin Reardon, Michael A. Faltys, Kevin J. Tracey, Tak W. Mak, William R. Parrish, Yousef Al-Abed, Peder S. Olofsson, Ulf Andersson, William M Hanes, Anna R. Drake |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine alpha7 Nicotinic Acetylcholine Receptor Inflammatory reflex Pharmacology Inbred C57BL Rats Sprague-Dawley Adenylyl cyclase Mice chemistry.chemical_compound 0302 clinical medicine adenylyl cyclase 6 2.1 Biological and endogenous factors Immunology and Allergy Aetiology Original Research sustained TNF inhibition Vagus Nerve CREB-Binding Protein Nicotinic agonist Medical Microbiology Tumor Necrosis Factors Tumor necrosis factor alpha medicine.symptom Acetylcholine Adenylyl Cyclases medicine.drug lcsh:Immunologic diseases. Allergy alpha 7nAChR 1.1 Normal biological development and functioning Immunology Inflammation Cell Line α7nAChR 03 medical and health sciences inflammatory reflex vagus nerve stimulation/VNS Underpinning research Reflex medicine Animals Macrophages Inflammatory and immune system Neurosciences choline acetyltransferase acetylcholine Rats Mice Inbred C57BL Endotoxins RAW 264.7 Cells 030104 developmental biology chemistry Macrophage cytokine production Cholinergic Sprague-Dawley lcsh:RC581-607 Spleen 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in immunology, vol 9, iss NOV Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.02648 |
| Popis: | Macrophage cytokine production is regulated by neural signals, for example in the inflammatory reflex. Signals in the vagus and splenic nerves are relayed by choline acetyltransferase+ T cells that release acetylcholine, the cognate ligand for alpha7 nicotinic acetylcholine subunit-containing receptors (α7nAChR), and suppress TNF release in macrophages. Here, we observed that electrical vagus nerve stimulation with a duration of 0.1–60 s significantly reduced systemic TNF release in experimental endotoxemia. This suppression of TNF was sustained for more than 24 h, but abolished in mice deficient in the α7nAChR subunit. Exposure of primary human macrophages and murine RAW 264.7 macrophage-like cells to selective ligands for α7nAChR for 1 h in vitro attenuated TNF production for up to 24 h in response to endotoxin. Pharmacological inhibition of adenylyl cyclase (AC) and knockdown of adenylyl cyclase 6 (AC6) or c-FOS abolished cholinergic suppression of endotoxin-induced TNF release. These findings indicate that action potentials in the inflammatory reflex trigger a change in macrophage behavior that requires AC and phosphorylation of the cAMP response element binding protein (CREB). These observations further our mechanistic understanding of neural regulation of inflammation and may have implications for development of bioelectronic medicine treatment of inflammatory diseases. |
| Databáze: | OpenAIRE |
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