TAT cell-penetrating peptide modulates inflammatory response and apoptosis in human lung epithelial cells.

Abstract

Cell-penetrating peptides (CPPs) are commonly used as delivery vehicles for the introduction of a variety of macromolecules into cells. Trans-activator of transcription (TAT) is the most commonly used CPP and, as a delivery vehicle, is assumed to be biologically inert. In this study, we pretreated human lung epithelial cells with TAT prior to stimulation with phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator. Surprisingly, TAT alone inhibited the production of multiple cytokines induced by PKC activation. Furthermore, PKC activation-induced IκBα degradation was partially reduced by TAT. Moreover, TAT treatment alone induced apoptosis in a dose-dependent manner, influenced expression of several B cell lymphoma 2 (Bcl-2) family members and increased caspase 3 cleavage at a high dose. These findings suggest that TAT as a delivery vehicle should be used cautiously, as it may affect the inflammatory response, as well as signals related to apoptosis.

• Authors: Hyunhee Kim, Serisha Moodley, Mingyao Liu
• Journal: Drug delivery and translational research (Drug Deliv Transl Res) Vol. 5 Issue 3 Pg. 275-8 (Jun 2015) ISSN: 2190-3948 [Electronic] United States
• PMID: 25916485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cell-Penetrating Peptides
• Cytokines
• Drug Carriers
• Enzyme Activators
• Gene Products, tat
• I-kappa B Proteins
• Immunotoxins
• NFKBIA protein, human
• Protective Agents
• NF-KappaB Inhibitor alpha
• Phorbol 12,13-Dibutyrate
• Protein Kinase C

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Cell-Penetrating Peptides (pharmacology)
• Cytokines (antagonists & inhibitors, metabolism)
• Drug Carriers (pharmacology)
• Enzyme Activators (chemistry, toxicity)
• Gene Products, tat (pharmacology)
• Humans
• I-kappa B Proteins (metabolism)
• Immunotoxins (chemistry, toxicity)
• Lung (drug effects, immunology, metabolism)
• NF-KappaB Inhibitor alpha
• Osmolar Concentration
• Phorbol 12,13-Dibutyrate (chemistry, toxicity)
• Protective Agents (pharmacology)
• Protein Kinase C (chemistry, metabolism)
• Proteolysis (drug effects)
• Respiratory Mucosa (drug effects, immunology, metabolism)
• Signal Transduction (drug effects)