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- Title
A G protein-coupled α7 nicotinic receptor regulates signaling and TNF-α release in microglia.
- Authors
King, Justin R.; Gillevet, Trudy C.; Kabbani, Nadine
- Abstract
Acetylcholine activation of α7 nicotinic acetylcholine receptors (α7 nAChRs) in microglia attenuates neuroinflammation and regulates TNF-α release. We used lipopolysaccharide to model inflammation in the microglial cell line EOC20 and examined signaling by the α7 nAChR. Co-immunoprecipitation experiments confirm that α7 nAChRs bind heterotrimeric G proteins in EOC20 cells. Interaction with Gαi mediates α7 nAChR signaling via enhanced intracellular calcium release and a decrease in cAMP, p38 phosphorylation, and TNF-α release. These α7 nAChR effects were blocked by the inhibition of Gαi signaling via pertussis toxin, PLC activity with U73122, and α7 nAChR channel activity with the selective antagonist α-bungarotoxin. Moreover, α7 nAChR signaling in EOC20 cells was significantly diminished by the expression of a dominant-negative α7 nAChR, α7345-8A, shown to be impaired in G protein binding. These findings indicate an essential role for G protein coupling in α7 nAChR function in microglia leading to the regulation of inflammation in the nervous system.
- Subjects
NICOTINIC acetylcholine receptors; MICROGLIA; PHYSIOLOGICAL effects of lipopolysaccharides; INFLAMMATION prevention; G proteins
- Publication
FEBS Open Bio, 2017, Vol 7, Issue 9, p1350
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.12270