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Titel: Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease
VerfasserIn: Schunk, Stefan J.
Triem, Sarah
Schmit, David
Zewinger, Stephen
Sarakpi, Tamim
Becker, Ellen
Hütter, Gregor
Wrublewsky, Selina
Küting, Fabienne
Hohl, Mathias
Alansary, Dalia
Prates Roma, Leticia
Lipp, Peter
Möllmann, Julia
Lehrke, Michael
Laschke, Matthias W.
Menger, Michael D.
Kramann, Rafael
Boor, Peter
Jahnen-Dechent, Willi
März, Winfried
Böhm, Michael
Laufs, Ulrich
Niemeyer, Barbara A.
Fliser, Danilo
Ampofo, Emmanuel
Speer, Thimoteus
Sprache: Englisch
Titel: Circulation
Bandnummer: 144
Heft: 11
Seiten: 893-908
Verlag/Plattform: Lippincott, Williams & Wilkins
Erscheinungsjahr: 2021
Freie Schlagwörter: chronic kidney disease
inflammation
interleukin-1α
leukocyte adhesion
myocardial infarction
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: BACKGROUND: Cardiovascular diseases and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin interleukin-1α (IL-1α) is expressed in a variety of cell types promoting (sterile) systemic inflammation. The aim of the present study was to examine the role of IL-1α in mediating inflammation in the setting of acute myocardial infarction (AMI) and CKD. METHODS: We assessed the expression of IL-1α on the surface of monocytes from patients with AMI and patients with CKD and determined its association with atherosclerotic cardiovascular disease events during follow-up in an explorative clinical study. Furthermore, we assessed the inflammatory effects of IL-1α in several organ injury models in Il1a−/− and Il1b−/− mice and investigated the underlying mechanisms in vitro in monocytes and endothelial cells. RESULTS: IL-1α is strongly expressed on the surface of monocytes from patients with AMI and CKD compared with healthy controls. Higher IL-1α surface expression on monocytes from patients with AMI and CKD was associated with a higher risk for atherosclerotic cardiovascular disease events, which underlines the clinical relevance of IL-1α. In mice, IL-1α, but not IL-1β, mediates leukocyte-endothelial adhesion as determined by intravital microscopy. IL-1α promotes accumulation of macrophages and neutrophils in inflamed tissue in vivo. Furthermore, IL-1α on monocytes stimulates their homing at sites of vascular injury. A variety of stimuli such as free fatty acids or oxalate crystals induce IL-1α surface expression and release by monocytes, which then mediates their adhesion to the endothelium via IL-1 receptor-1. IL-1α also promotes expression of the VCAM-1 (vascular cell adhesion molecule-1) on endothelial cells, thereby fostering the adhesion of circulating leukocytes. IL-1α induces inflammatory injury after experimental AMI, and abrogation of IL-1α prevents the development of CKD in oxalate or adenine-fed mice. CONCLUSIONS: IL-1α represents a key mediator of leukocyte-endothelial adhesion and inflammation in AMI and CKD. Inhibition of IL-1α may serve as a novel anti-inflammatory treatment strategy.
DOI der Erstveröffentlichung: 10.1161/CIRCULATIONAHA.121.053547
URL der Erstveröffentlichung: https://doi.org/10.1161/CIRCULATIONAHA.121.053547
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-423700
hdl:20.500.11880/38032
http://dx.doi.org/10.22028/D291-42370
ISSN: 1524-4539
0009-7322
Datum des Eintrags: 11-Jul-2024
Bezeichnung des in Beziehung stehenden Objekts: Supplemental Material
In Beziehung stehendes Objekt: https://www.ahajournals.org/doi/suppl/10.1161/CIRCULATIONAHA.121.053547/suppl_file/10.1161.circulationaha.121.053547%20data%20supplement.pdf
https://www.ahajournals.org/doi/suppl/10.1161/CIRCULATIONAHA.121.053547/suppl_file/circ_circulationaha-2021-053547_supp1.pdf
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Anatomie und Zellbiologie
M - Biophysik
M - Chirurgie
M - Innere Medizin
Professur: M - Prof. Dr. Michael Böhm
M - Prof. Dr. Danilo Fliser
M - Prof. Dr. Ulrich Laufs
M - Prof. Dr. Michael D. Menger
M - Prof. Dr. Barbara Niemeyer
M - Jun.-Prof. Dr. Leticia Prates Roma
M - Dr. med. Dr. sc.nat. Timo Speer
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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