The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

Morten Skøtt Thomsen; Jens D Mikkelsen

doi:10.1016/j.jneuroim.2012.07.006

The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

82 Citations (Scopus)

Abstract

The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (

Original language	English
Journal	Journal of Neuroimmunology
Volume	251
Issue number	1-2
Pages (from-to)	65-72
Number of pages	8
DOIs	https://doi.org/10.1016/j.jneuroim.2012.07.006
Publication status	Published - 15 Oct 2012

Keywords

Aconitine
Animals
Anti-Inflammatory Agents
Azabicyclo Compounds
Benzylidene Compounds
Furans
Lipopolysaccharides
MAP Kinase Signaling System
Male
Microglia
Nicotinic Agonists
Nicotinic Antagonists
Pyridines
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic
Tumor Necrosis Factor-alpha
alpha7 Nicotinic Acetylcholine Receptor

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10.1016/j.jneuroim.2012.07.006

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title = "The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia",

abstract = "The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (",

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T1 - The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

AU - Thomsen, Morten Skøtt

AU - Mikkelsen, Jens D

PY - 2012/10/15

Y1 - 2012/10/15

N2 - The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (

AB - The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (

KW - Aconitine

KW - Animals

KW - Anti-Inflammatory Agents

KW - Azabicyclo Compounds

KW - Benzylidene Compounds

KW - Furans

KW - Lipopolysaccharides

KW - MAP Kinase Signaling System

KW - Male

KW - Microglia

KW - Nicotinic Agonists

KW - Nicotinic Antagonists

KW - Pyridines

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Nicotinic

KW - Tumor Necrosis Factor-alpha

KW - alpha7 Nicotinic Acetylcholine Receptor

U2 - 10.1016/j.jneuroim.2012.07.006

DO - 10.1016/j.jneuroim.2012.07.006

M3 - Journal article

C2 - 22884467

SN - 1872-8421

VL - 251

SP - 65

EP - 72

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

Abstract

Keywords

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