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dc.contributor.authorHollenhorst, Monika I
dc.contributor.authorJurastow, Innokentij
dc.contributor.authorNandigama, Rajender
dc.contributor.authorAppenzeller, Silke
dc.contributor.authorLi, Lei
dc.contributor.authorVogel, Jörg
dc.contributor.authorWiederhold, Stephanie
dc.contributor.authorAlthaus, Mike
dc.contributor.authorEmpting, Martin
dc.contributor.authorAltmüller, Janine
dc.contributor.authorHirsch, Anna K H
dc.contributor.authorFlockerzi, Veit
dc.contributor.authorCanning, Brendan J
dc.contributor.authorSaliba, Antoine-Emmanuel
dc.contributor.authorKrasteva-Christ, Gabriela
dc.date.accessioned2020-01-17T12:55:58Z
dc.date.available2020-01-17T12:55:58Z
dc.date.issued2020-01-01
dc.identifier.citationFASEB J. 2020 Jan;34(1):316-332. doi: 10.1096/fj.201901314RR. Epub 2019 Nov 22.en_US
dc.identifier.issn1530-6860
dc.identifier.pmid31914675
dc.identifier.doi10.1096/fj.201901314RR
dc.identifier.urihttp://hdl.handle.net/10033/622090
dc.description.abstractFor protection from inhaled pathogens many strategies have evolved in the airways such as mucociliary clearance and cough. We have previously shown that protective respiratory reflexes to locally released bacterial bitter "taste" substances are most probably initiated by tracheal brush cells (BC). Our single-cell RNA-seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (Tas2r108, Gnat3, Trpm5). We directly demonstrate the secretion of acetylcholine (ACh) from BC upon stimulation with the Tas2R agonist denatonium. Inhibition of the taste transduction cascade abolished the increase in [Ca2+]i in BC and subsequent ACh-release. ACh-release is regulated in an autocrine manner. While the muscarinic ACh-receptors M3R and M1R are activating, M2R is inhibitory. Paracrine effects of ACh released in response to denatonium included increased [Ca2+]i in ciliated cells. Stimulation by denatonium or with Pseudomonas quinolone signaling molecules led to an increase in mucociliary clearance in explanted tracheae that was Trpm5- and M3R-mediated. We show that ACh-release from BC via the bitter taste cascade leads to immediate paracrine protective responses that can be boosted in an autocrine manner. This mechanism represents the initial step for the activation of innate immune responses against pathogens in the airways.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectacetylcholineen_US
dc.subjectbrush cellsen_US
dc.subjectmucociliary clearanceen_US
dc.subjectsingle‐cell RNA‐seqen_US
dc.subjecttasteen_US
dc.titleTracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalFASEB Journalen_US
refterms.dateFOA2020-01-17T12:55:59Z
dc.source.journaltitleFASEB journal : official publication of the Federation of American Societies for Experimental Biology


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