An IRF5 Decoy Peptide Reduces Myocardial Inflammation and Fibrosis and Improves Endothelial Cell Function in Tight-Skin Mice.

Autor: Dorothee Weihrauch, John G Krolikowski, Deron W Jones, Tahniyath Zaman, Omoshalewa Bamkole, Janine Struve, Savin Pillai, Paul S Pagel, Nicole L Lohr, Kirkwood A Pritchard
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: PLoS ONE, Vol 11, Iss 4, p e0151999 (2016)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0151999
Popis: Interferon regulatory factor 5 (IRF5) has been called a "master switch" for its ability to determine whether cells mount proinflammatory or anti-inflammatory responses. Accordingly, IRF5 should be an attractive target for therapeutic drug development. Here we report on the development of a novel decoy peptide inhibitor of IRF5 that decreases myocardial inflammation and improves vascular endothelial cell (EC) function in tight-skin (Tsk/+) mice. Biolayer interferometry studies showed the Kd of IRF5D for recombinant IRF5 to be 3.72 ± 0.74x10-6M. Increasing concentrations of IRF5D (0-100 μg/mL, 24h) had no significant effect on EC proliferation or apoptosis. Treatment of Tsk/+ mice with IRF5D (1mg/kg/d subcutaneously, 21d) reduced IRF5 and ICAM-1 expression and monocyte/macrophage and neutrophil counts in Tsk/+ hearts compared to expression in hearts from PBS-treated Tsk/+ mice (p
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