Journal article

Authors list: Richter, K; Ogiemwonyi-Schaefer, R; Wilker, S; Chaveiro, AI; Agné, A; Hecker, M; Reichert, M; Amati, AL; Schlüter, KD; Manzini, I; Schmalzing, G; McIntosh, JM; Padberg, W; Grau, V; Hecker, A

Publication year: 2020

Journal: Journal of Clinical Medicine

Volume number: 9

Issue number: 9

eISSN: 2077-0383

Open access status: Gold

DOI Link: https://doi.org/10.3390/jcm9092887

Publisher: MDPI

Abstract: 
Amyloid-beta peptide (A beta(1-42)), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer's disease. A beta(1-42)can induce the secretion of the pro-inflammatory cytokine intereukin-1 beta (IL-1 beta) in immune cells within and out of the nervous system. Known interaction partners of A beta(1-42)are alpha 7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of A beta(1-42)are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1 beta by canonical and non-canonical agonists of nAChRs containing subunits alpha 7, alpha 9, and/or alpha 10. Here, we tested the hypothesis that A beta(1-42)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 A beta(1-42). IL-1 beta concentrations were measured in the supernatant. A beta(1-42)dose-dependently (IC50= 2.54 mu M) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1 beta-release by monocytic cells, whereas reverse A beta(42-1)was ineffective. In conclusion, we discovered a novel pro-inflammatory A beta(1-42)function that enables monocytic IL-1 beta release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of A beta(1-42)in the context of sterile systemic inflammation.

Harvard Citation style: Richter, K., Ogiemwonyi-Schaefer, R., Wilker, S., Chaveiro, A., Agné, A., Hecker, M., et al. (2020) Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release , Journal of Clinical Medicine, 9(9), Article 2887. https://doi.org/10.3390/jcm9092887

APA Citation style: Richter, K., Ogiemwonyi-Schaefer, R., Wilker, S., Chaveiro, A., Agné, A., Hecker, M., Reichert, M., Amati, A., Schlüter, K., Manzini, I., Schmalzing, G., McIntosh, J., Padberg, W., Grau, V., & Hecker, A. (2020). Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release . Journal of Clinical Medicine. 9(9), Article 2887. https://doi.org/10.3390/jcm9092887