{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:00Z","timestamp":1787026620654,"version":"build-2736575974"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["515250365, 528562393-FIP 26"],"award-info":[{"award-number":["515250365, 528562393-FIP 26"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021213","name":"LOEWE-Zentrum f\u00fcr Translationale Medizin und Pharmakologie","doi-asserted-by":"publisher","award":["FLOW FOR LIFE"],"award-info":[{"award-number":["FLOW FOR LIFE"]}],"id":[{"id":"10.13039\/501100021213","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM136430"],"award-info":[{"award-number":["R35 GM136430"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The clinical interest in mechanisms controlling the biosynthesis and release of the pro-inflammatory cytokine interleukin (IL)-1\u03b2 is outstanding, as IL-1\u03b2 is associated with life-threatening inflammatory diseases including hyperinflammation caused by extracellular ATP originating from damaged cells. Previously, we identified a cholinergic mechanism controlling ATP-dependent IL-1\u03b2 release via metabotropic signaling of unconventional nicotinic acetylcholine receptors (nAChRs) containing subunits \u03b17 and \u03b19* (denoting homomeric or heteromeric \u03b19) in monocytes. This study examines whether this mechanism is active in human macrophages (THP-1 cell-derived, peripheral blood mononuclear cell-derived, and peritoneal macrophages).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Expression of nAChR subtypes (\n                      <jats:italic>CHRNA7<\/jats:italic>\n                      ,\n                      <jats:italic>CHRFAM7A<\/jats:italic>\n                      ,\n                      <jats:italic>CHRNA9<\/jats:italic>\n                      ,\n                      <jats:italic>CHRNA10<\/jats:italic>\n                      ) was analyzed using real-time RT-PCR. The efficiency of the differentiation protocols used was assessed by surface markers and metabolic conversion rate analysis. Cholinergic control of ATP-induced IL-1\u03b2, IL-18, and IL-1\u03b1 release was tested using nAChR agonists and conopeptides antagonizing \u03b17 and \u03b19* nAChRs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All nAChR subunits were expressed by all cells analyzed. Activation of nAChRs efficiently inhibited the ATP-mediated IL-1\u03b2 release by macrophages, while ATP-independent release remained unaffected. Moreover, the nAChR agonists inhibited the release of IL-18 and IL-1\u03b1. The inhibitory effect was reversed by subunit-specific conopeptides, indicating the involvement of unconventional nAChRs containing subunits \u03b17 and \u03b19*.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We conclude that the cholinergic control of ATP-mediated IL-1\u03b2 release is active in human monocytes and in macrophages and that nAChR agonists can also regulate the release of IL-18 and IL-1\u03b1. This mechanism specifically regulates the ATP-induced cytokine release, without suppressing ATP-independent cytokine release. Thus, unconventional \u03b19* nAChRs are promising therapeutic targets for ATP-induced inflammatory diseases, including sterile hyperinflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1661114","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T14:29:13Z","timestamp":1761575353000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The ATP-mediated cytokine release by macrophages is down-modulated by unconventional \u03b19* nicotinic acetylcholine receptors"],"prefix":"10.3389","volume":"16","author":[{"given":"Philipp M. 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