TAT cell-penetrating peptide modulates inflammatory response and apoptosis in human lung epithelial cells.
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.
Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute University Health Network, Toronto, Ontario, Canada.
Hyunhee
H
Kim
Serisha
S
Moodley
Mingyao
M
Liu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D004337:Drug Carriers / Q000494:pharmacology; D020536:Enzyme Activators / Q000737:chemistry / Q000633:toxicity; D015696:Gene Products, tat / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D000922:Immunotoxins / Q000737:chemistry / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D009994:Osmolar Concentration; D015240:Phorbol 12,13-Dibutyrate / Q000737:chemistry / Q000633:toxicity; D020011:Protective Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D057846:Cell-Penetrating Peptides; D016207:Cytokines; D004337:Drug Carriers; D020536:Enzyme Activators; D015696:Gene Products, tat; D020672:I-kappa B Proteins; D000922:Immunotoxins; C000606204:NFKBIA protein, human; D020011:Protective Agents; D000072000:NF-KappaB Inhibitor alpha; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C