In vitro and in vivo nuclear factor-kappaB inhibitory effects of the cell-penetrating penetratin peptide

Molecular Pharmacology
Tamás LetohaErno Duda

Abstract

Penetratin is a cationic cell-penetrating peptide that has been frequently used for the intracellular delivery of polar bioactive compounds. Recent studies have just revealed the major role of polyanionic membrane proteoglycans and cholesterol-enriched lipid rafts in the uptake of the peptide. Both proteoglycans and lipid-rafts influence inflammatory processes by binding a wide array of proinflammatory mediators; thus, we decided to analyze the effect of penetratin on in vitro and in vivo inflammatory responses. Our in vitro luciferase gene assays demonstrated that penetratin decreased transcriptional activity of nuclear factor-kappaB (NF-kappaB) in tumor necrosis factor (TNF)-stimulated L929 fibroblasts and lipopolysaccharide-activated RAW 264.7 macrophages. Penetratin also inhibited TNF-induced intercellular adhesion molecule-1 expression in human endothelial HMEC-1 cells. Exogenous heparan sulfate abolished the in vitro NF-kappaB inhibitory effects of the peptide. Uptake experiments showed that penetratin was internalized by all of the above-mentioned cell lines in vitro and rapidly entered the cells of the lung and pancreas in vivo. In an in vivo rat model of acute pancreatitis, a disease induced by elevated activities of s...Continue Reading

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Citations

May 11, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yu Fu WangHua-Ping Liang
Jan 12, 2013·Current Protein & Peptide Science·Ota FekonjaRoman Jerala
Apr 7, 2016·Cellular and Molecular Life Sciences : CMLS·Stefan KrautwaldUlrich Kunzendorf
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Aug 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Monika AvbeljRoman Jerala

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