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

Autor: Janine A. Struve, Kirkwood A. Pritchard, John G. Krolikowski, Tahniyath Zaman, Savin Pillai, Nicole L. Lohr, Dorothee Weihrauch, Omoshalewa Bamkole, Deron W. Jones, Paul S. Pagel
Rok vydání: 2016
Předmět:
0301 basic medicine
Protein Conformation
lcsh:Medicine
Apoptosis
Vasodilation
Pathology and Laboratory Medicine
Biochemistry
Mice
0302 clinical medicine
Animal Cells
Fibrosis
Medicine and Health Sciences
Post-Translational Modification
Phosphorylation
lcsh:Science
Immune Response
Multidisciplinary
Cell Death
Heart
Animal Models
Endothelial stem cell
Myocarditis
Protein Transport
medicine.anatomical_structure
Cell Processes
030220 oncology & carcinogenesis
Interferon Regulatory Factors
Anatomy
Cellular Types
medicine.symptom
Research Article
medicine.medical_specialty
Endothelium
Inflammatory Diseases
Immunology
Muscle Tissue
Mouse Models
Inflammation
Biology
Research and Analysis Methods
Proinflammatory cytokine
03 medical and health sciences
Model Organisms
Signs and Symptoms
Diagnostic Medicine
Internal medicine
medicine
Animals
Cell Nucleus
Muscle Cells
Monocyte
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
medicine.disease
Mice
Inbred C57BL
Biological Tissue
030104 developmental biology
Endocrinology
Cardiovascular Anatomy
lcsh:Q
Endothelium
Vascular
Peptides
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 4, p e0151999 (2016)
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
Databáze: OpenAIRE
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