Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Siebers, Kathrin [VerfasserIn]   i
 Chamulitrat, Walee [VerfasserIn]   i
Titel:Alpha-1 antitrypsin inhibits ATP-mediated release of interleukin-1β via CD36 and nicotinic acetylcholine receptors
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
E-Jahr:2018
Jahr:25 April 2018
Umfang:15 S.
Fussnoten:Gesehen am 01.10.2019
Titel Quelle:Enthalten in: Frontiers in immunology
Ort Quelle:Lausanne : Frontiers Media, 2010
Jahr Quelle:2018
Band/Heft Quelle:9(2018) Artikel-Nummer 877, 15 Seiten
ISSN Quelle:1664-3224
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.
DOI:doi:10.3389/fimmu.2018.00877
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
 DOI: https://doi.org/10.3389/fimmu.2018.00877
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Adenosine Triphosphate
 alpha 1-Antitrypsin
 Animals
 calcium-independent phospholipase A2β
 CD36
 CD36 Antigens
 CHRNA10
 CHRNA7
 CHRNA9
 Humans
 inflammasome
 Inflammasomes
 Interleukin-1beta
 interleukin-1β
 Leukocytes, Mononuclear
 P2X7 receptor
 Primary Cell Culture
 Rats
 Receptors, Purinergic P2X7
 Systemic Inflammatory Response Syndrome
 U937 Cells
K10plus-PPN:1677982012
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68434566   QR-Code
zum Seitenanfang