Amyloid Beta Peptide (Aß1-42) Reverses the Cholinergic Control of Monocytic IL-1ß Release.
J Clin Med
; 9(9)2020 Sep 07.
Article
en En
| MEDLINE
| ID: mdl-32906646
ABSTRACT
Amyloid-ß peptide (Aß1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer's disease. Aß1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1ß (IL-1ß) in immune cells within and out of the nervous system. Known interaction partners of Aß1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aß1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1ß by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aß1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aß1-42. IL-1ß concentrations were measured in the supernatant. Aß1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1ß-release by monocytic cells, whereas reverse Aß42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aß1-42 function that enables monocytic IL-1ß release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aß1-42 in the context of sterile systemic inflammation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Clin Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
CH
/
SUIZA
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SUÍÇA
/
SWITZERLAND