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

Tamás Letoha, E. Kúsz, Gábor Pápai, Annamária Szabolcs, J. Kaszaki, I. Varga, T. Takács, B. Penke, E. Duda

Research output: Contribution to journalArticle

20 Citations (Scopus)

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-κB (NF-κB) 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-κB 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 stress-responsive transcription factors like NF-κB, pretreatment with only 2 mg/kg penetratin attenuated the severity of pancreatic inflammation by interfering with IκB degradation and subsequent nuclear import of NF-κB, inhibiting the expression of proinflammatory genes and improving the monitored laboratory and histological parameters of pancreatitis and associated oxidative stress.

Original languageEnglish
Pages (from-to)2027-2036
Number of pages10
JournalMolecular Pharmacology
Volume69
Issue number6
DOIs
Publication statusPublished - 2006

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Cell-Penetrating Peptides
Proteoglycans
Pancreatitis
Tumor Necrosis Factor-alpha
Lipids
Peptides
Heparitin Sulfate
Cell Nucleus Active Transport
Intercellular Adhesion Molecule-1
Luciferases
Lipopolysaccharides
In Vitro Techniques
penetratin
Pancreas
Oxidative Stress
Transcription Factors
Fibroblasts
Macrophages
Cholesterol
Inflammation

ASJC Scopus subject areas

  • Pharmacology

Cite this

In vitro and in vivo nuclear factor-κB inhibitory effects of the cell-penetrating penetratin peptide. / Letoha, Tamás; Kúsz, E.; Pápai, Gábor; Szabolcs, Annamária; Kaszaki, J.; Varga, I.; Takács, T.; Penke, B.; Duda, E.

In: Molecular Pharmacology, Vol. 69, No. 6, 2006, p. 2027-2036.

Research output: Contribution to journalArticle

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