{"doi":"10.3390/jcm9092887","title":"Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release","abstract":"Amyloid-β peptide (Aβ1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of the nervous system. Known interaction partners of Aβ1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aβ1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1β by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aβ1-42 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 Aβ1-42. IL-1β concentrations were measured in the supernatant. Aβ1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1β-release by monocytic cells, whereas reverse Aβ42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aβ1-42 function that enables monocytic IL-1β release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aβ1-42 in the context of sterile systemic inflammation.","journal":"Journal of Clinical Medicine","year":2020,"id":88439,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":448644,"name":"Raymond Ogiemwonyi‐Schaefer","orcid":"0000-0002-7993-2307","position":1,"is_corresponding":false},{"id":449961,"name":"Sigrid Wilker","orcid":null,"position":2,"is_corresponding":false},{"id":449962,"name":"Anna I. Chaveiro","orcid":null,"position":3,"is_corresponding":false},{"id":449963,"name":"Alisa Agné","orcid":null,"position":4,"is_corresponding":false},{"id":448645,"name":"Matthias Hecker","orcid":"0000-0003-0614-5967","position":5,"is_corresponding":false},{"id":448646,"name":"Martin Reichert","orcid":"0000-0003-0795-0941","position":6,"is_corresponding":false},{"id":449964,"name":"Anca‐Laura Amati","orcid":null,"position":7,"is_corresponding":false},{"id":448647,"name":"Klaus‐Dieter Schlüter","orcid":"0000-0002-6093-4919","position":8,"is_corresponding":false},{"id":405017,"name":"Ivan Manzini","orcid":"0000-0002-3575-9637","position":9,"is_corresponding":false},{"id":74469,"name":"Günther Schmalzing","orcid":null,"position":10,"is_corresponding":false},{"id":356823,"name":"J. Michael McIntosh","orcid":"0000-0001-9939-7981","position":11,"is_corresponding":false},{"id":448648,"name":"Winfried Padberg","orcid":"0000-0002-1349-6784","position":12,"is_corresponding":false},{"id":448649,"name":"Veronika Grau","orcid":"0000-0001-7512-2051","position":13,"is_corresponding":false},{"id":448650,"name":"Andreas Hecker","orcid":"0000-0002-7704-7494","position":14,"is_corresponding":false},{"id":448643,"name":"Katrin Richter","orcid":"0000-0002-2450-1083","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T22:01:22.387926Z","pmid":"32906646","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}