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Medientyp:
E-Artikel
Titel:
IL-1β neutralization prevents diastolic dysfunction development, but lacks hepatoprotective effect in an aged mouse model of NASH
Beteiligte:
Kucsera, Dániel;
Tóth, Viktória E.;
Sayour, Nabil V.;
Kovács, Tamás;
Gergely, Tamás G.;
Ruppert, Mihály;
Radovits, Tamás;
Fábián, Alexandra;
Kovács, Attila;
Merkely, Béla;
Ferdinandy, Péter;
Varga, Zoltán V.
Erschienen:
Springer Science and Business Media LLC, 2023
Erschienen in:Scientific Reports
Sprache:
Englisch
DOI:
10.1038/s41598-022-26896-3
ISSN:
2045-2322
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies. We aimed to investigate the hepatic and cardiac effects of an IL-1β targeting monoclonal antibody in an aged mouse model of NASH. 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1β Mab for 8 weeks. Cardiac functions were assessed by conventional—and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR. Echocardiography revealed improved cardiac diastolic function in anti-IL-1β treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1β inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1β inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1β. IL-1β inhibition increased hepatic expression of <jats:italic>Pd-1</jats:italic> and <jats:italic>Ctla4</jats:italic>, while <jats:italic>Pd-l1</jats:italic> expression increased in NASH. In conclusion, IL-1β inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.</jats:p>