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| Verfasst von: | Siebers, Kathrin [VerfasserIn]  |
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| | Chamulitrat, Walee [VerfasserIn] |
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| Titel: | Alpha-1 antitrypsin inhibits ATP-mediated release of interleukin-1β via CD36 and nicotinic acetylcholine receptors |
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| Verf.angabe: | Kathrin Siebers, Bijan Fink, Anna Zakrzewicz, Alisa Agné, Katrin Richter, Sebastian Konzok, Andreas Hecker, Sven Zukunft, Mira Küllmar, Jochen Klein, J. Michael McIntosh, Thomas Timm, Katherina Sewald, Winfried Padberg, Nupur Aggarwal, Walee Chamulitrat, Sentot Santoso, Wendy Xia, Sabina Janciauskiene and Veronika Grau |
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| E-Jahr: | 2018 |
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| Jahr: | 25 April 2018 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 01.10.2019 |
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| Titel Quelle: | Enthalten in: Frontiers in immunology |
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| Ort Quelle: | Lausanne : Frontiers Media, 2010 |
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| Jahr Quelle: | 2018 |
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| Band/Heft Quelle: | 9(2018) Artikel-Nummer 877, 15 Seiten |
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| ISSN Quelle: | 1664-3224 |
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| Abstract: | While interleukin (IL)-1β 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-1β 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-1β. The human anti-protease alpha-1 antitrypsin (AAT) and IL-1β regulate each other via mechanisms that are only partially understood. Here, we demonstrate that physiological concentrations of AAT efficiently inhibit ATP-induced release of IL-1β from primary human blood mononuclear cells, monocytic U937 cells, and rat lung tissue, whereas ATP-independent IL-1β release is not impaired. Both, native and oxidized AAT are active, suggesting that the inhibition of IL-1β release is independent of the anti-elastase activity of AAT. Signaling of AAT 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 AAT controls ATP-induced IL-1β 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. |
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| DOI: | doi:10.3389/fimmu.2018.00877 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: http://dx.doi.org/10.3389/fimmu.2018.00877 |
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| | DOI: https://doi.org/10.3389/fimmu.2018.00877 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Adenosine Triphosphate |
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| | alpha 1-Antitrypsin |
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| | Animals |
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| | calcium-independent phospholipase A2β |
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| | CD36 |
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| | CD36 Antigens |
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| | CHRNA10 |
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| | CHRNA7 |
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| | CHRNA9 |
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| | Humans |
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| | inflammasome |
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| | Inflammasomes |
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| | Interleukin-1beta |
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| | interleukin-1β |
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| | Leukocytes, Mononuclear |
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| | P2X7 receptor |
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| | Primary Cell Culture |
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| | Rats |
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| | Receptors, Purinergic P2X7 |
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| | Systemic Inflammatory Response Syndrome |
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| | U937 Cells |
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| K10plus-PPN: | 1677982012 |
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| Verknüpfungen: | → Zeitschrift |
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Alpha-1 antitrypsin inhibits ATP-mediated release of interleukin-1β via CD36 and nicotinic acetylcholine receptors / Siebers, Kathrin [VerfasserIn]; 25 April 2018 (Online-Ressource)
