title: IL-1β suppresses TGF-β-mediated myofibroblast differentiation in cardiac fibroblasts.
abstract: Cardiac fibrosis is a maladaptive response of the injured myocardium and is mediated through a complex interplay between molecular triggers and cellular responses. Interleukin (IL)-1β is a key inflammatory inducer in cardiac disease and promotes cell invasion and cardiomyocyte injury, but little is known of its impact on fibrosis. A major cornerstone of fibrosis is the differentiation of cardiac fibroblasts (CFs) into myofibroblasts (myoFbs), which is highly promoted by Transforming Growth Factor (TGF)-β. Therefore, we asked how IL-1β functionally modulated CF-to-myoFb differentiation. Using a differentiation model of ventricular fibroblasts, we found that IL-1β instigated substantial anti-fibrogenic effects. In specific, IL-1β reduced proliferation, matrix activity, cell motility and α-smooth muscle actin expression, which are all hallmarks of myoFb differentiation. These findings suggest that IL-1β, besides from its acknowledged adverse role in the inflammatory response, can also exert beneficial effects in cardiac fibrosis by actively suppressing differentiation of CFs into fibrogenic myoFbs.
authors.affiliation: Laboratory for Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital and Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Hasse
authors.initials: H
authors.lastname: Brønnum
authors.forename: Tilde
authors.initials: T
authors.lastname: Eskildsen
authors.forename: Ditte Caroline
authors.initials: DC
authors.lastname: Andersen
authors.forename: Mikael
authors.initials: M
authors.lastname: Schneider
authors.forename: Søren Paludan
authors.initials: SP
authors.lastname: Sheikh
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000199:Actins; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta