Interacting with α 7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages.
Acta Pharm Sin B
; 10(10): 1926-1942, 2020 Oct.
Article
en En
| MEDLINE
| ID: mdl-33163344
ABSTRACT
Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.
ACh, acetylcholine; AChE; AChE, acetylcholinesterase; BChE, butyrylcholinesterase; CAP pathway, cholinergic anti-inflammatory pathway; CDC42, cell division cycle; ChAT, choline acetyltransferase; Cholinergic anti-inflammatory pathway; DPZ, donepezil; GAL, galantamine hydrobromide; IL, interleukin; LPS, lipopolysaccharides; MLA, methyllycaconitine citrate salt; MMP, matrix metalloproteinase; Macrophage; NF-κB, nuclear factor-κB; PHA, PHA-543613; PRiMA, proline-rich membrane anchor; TNF-α, tumor necrosis factor α; nAChR, nicotinic AChR; α7 nAChR
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Acta Pharm Sin B
Año:
2020
Tipo del documento:
Article
País de afiliación:
China