Alpha-1 Antitrypsin Inhibits ATP-Mediated Release of Interleukin-1beta via CD36 and Nicotinic Acetylcholine Receptors
dc.contributor.author | Siebers, Kathrin | |
dc.contributor.author | Fink, Bijan | |
dc.contributor.author | Zakrzewicz, Anna | |
dc.contributor.author | Agne, Alisa | |
dc.contributor.author | Richter, Katrin | |
dc.contributor.author | Konzok, Sebastian | |
dc.contributor.author | Hecker, Andreas | |
dc.contributor.author | Zukunft, Sven | |
dc.contributor.author | Küllmar, Mira | |
dc.contributor.author | Klein, Jochen | |
dc.contributor.author | McIntosh, J. Michael | |
dc.contributor.author | Timm, Thomas | |
dc.contributor.author | Sewald, Katherina | |
dc.contributor.author | Padberg, Winfried | |
dc.contributor.author | Aggarwal, Nupur | |
dc.contributor.author | Chamulitrat, Walee | |
dc.contributor.author | Santoso, Sentot | |
dc.contributor.author | Xia, Wendy | |
dc.contributor.author | Janciauskiene, Sabina | |
dc.contributor.author | Grau, Veronika | |
dc.date.accessioned | 2022-11-18T09:53:50Z | |
dc.date.available | 2019-05-20T14:47:17Z | |
dc.date.available | 2022-11-18T09:53:50Z | |
dc.date.issued | 2018 | |
dc.description.abstract | While interleukin (IL)-1beta is a potent pro-inflammatory cytokine involved in host defense, high levels can cause life-threatening sterile inflammation including systemic inflammatory response syndrome. Hence, the control of IL-1beta secretion is of outstanding biomedical importance. In response to a first inflammatory stimulus such as lipopolysaccharide, pro-IL-1β is synthesized as a cytoplasmic inactive pro-form. Extracellular ATP originating from injured cells is a prototypical second signal for inflammasome-dependent maturation and release of IL-1beta. The human anti-protease alpha-1 antitrypsin and IL-1beta regulate each other via mechanisms that are only partially understood. Here, we demonstrate that physiological concentrations of alpha-1 antitrypsin efficiently inhibit ATP-induced release of IL-1beta from primary human blood mononuclear cells, monocytic U937 cells and rat lung tissue, whereas ATP-independent IL-1beta release is not impaired. Both, native and oxidized alpha-1 antitrypsin are active, suggesting that the inhibition of IL-1beta release is independent of the anti-elastase activity of alpha-1 antitrypsin. Signaling of alpha-1 antitrypsin in monocytic cells involves the lipid scavenger receptor CD36, calcium-independent phospholipase A2β and the release of a small soluble mediator. This mediator leads to the activation of nicotinic acetylcholine receptors, which efficiently inhibit ATP-induced P2X7 receptor activation and inflammasome assembly. We suggest that alpha-1 antitrypsin controls ATP-induced IL-1beta release from human mononuclear blood cells by a novel triple-membrane-passing signaling pathway. This pathway may have clinical implications for the prevention of sterile pulmonary and systemic inflammation. | en |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-146306 | |
dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/9465 | |
dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-8853 | |
dc.language.iso | en | de_DE |
dc.rights | Namensnennung 4.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | CD36 | en |
dc.subject | CHRNA7 | en |
dc.subject | CHRNA9 | en |
dc.subject | CHRNA10 | en |
dc.subject | inflammasome | en |
dc.subject.ddc | ddc:610 | de_DE |
dc.title | Alpha-1 Antitrypsin Inhibits ATP-Mediated Release of Interleukin-1beta via CD36 and Nicotinic Acetylcholine Receptors | en |
dc.type | article | de_DE |
local.affiliation | FB 11 - Medizin | de_DE |
local.opus.fachgebiet | Medizin | de_DE |
local.opus.id | 14630 | |
local.opus.institute | Department of General and Thoracic Surgery | de_DE |
local.source.freetext | Frontiers in Immunology 9(877) | de_DE |
local.source.uri | https://doi.org/10.3389/fimmu.2018.00877 |
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