1 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU2 Clinical Biochemistry, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU3 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.4 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU5 Clinical Biochemistry, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
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.