• Magdalena Dziemidowicz, Tomasz A Bonda, Siergiej Litvinovich, Andrzej Taranta, Maria M Winnicka, and Karol A Kamiński.
• Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland.
• Arch Med Sci. 2019 Oct 1; 15 (6): 1565-1575.

IntroductionInflammatory mediators play an important role in development and progression of cardiovascular disease. Both adrenergic stimulation and high levels of interleukin-6 (IL-6) indicate an unfavorable outcome in patients with myocardial infarction or heart failure. Understanding the interaction between β-adrenergic stimulation and IL-6 in the myocardium may contribute to developing more effective treatments. The aim of this study was to verify the role of IL-6 in the effects of β-adrenergic stimulation in activating selected intracellular signaling pathways in mouse myocardium.Material And MethodsExperiments were performed on 12-week-old male mice: 16 C57BL/6JIL6‑/‑TMKopf (IL-6 KO) and 17 C57BL/6J (WT). Animals received intraperitoneal injections of isoproterenol (ISO, 50 mg/kg) or placebo (0.9% NaCl) once a day for 16 days. The phosphorylation of STAT3 (signal transducer and activator of transcription 3), ERK1/2 (extracellular-regulated kinases 1/2), Akt1/2/3, p-38, c-Raf and expression of SOCS3 (suppressor of cytokine signaling 3), PIAS1/3 (protein inhibitors of activated STAT) was assessed by western blotting in the myocardium 24 h after the last injection. Evaluation of gene expression downstream of these pathways was performed by real-time PCR.ResultsChronic ISO treatment leads to increased fibrosis of the myocardium in mice lacking IL-6, which is accompanied by increased activity of ERK1/2, p38 and reduced expression of SOCS3. Administration of ISO in IL-6 KO animals intensified gene expression of proteins activated by MAPK/ERK (myc; CEBPB; BMP4; Fasn; Tank), while it reduced expression of genes repressed by ERK 1/2 (Wisp1, Wnt1).ConclusionsIL-6 plays an important role in regulating the activation of MAPK pathways in the mouse myocardium in response to chronic β-adrenergic stimulation.Copyright: © 2019 Termedia & Banach.

6 keywords...

hide…