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

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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.

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Acknowledgments

This study was supported by Canadian Institutes of Health Research operating grants (MOP-42546 and MOP-119514).

Conflict of interest

Authors declare that they have no conflict of interest.

Animal studies

No animal or human studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute University Health Network, Toronto, Ontario, Canada

    Hyunhee Kim, Serisha Moodley & Mingyao Liu

  2. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

    Hyunhee Kim & Mingyao Liu

  3. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Serisha Moodley & Mingyao Liu

  4. Department of Surgery, Faculty of Medicine, University of Toronto, 101 College Street, Room TMDT 2-814, Toronto, Ontario, M5G 1L7, Canada

    Mingyao Liu

Authors
  1. Hyunhee Kim
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  2. Serisha Moodley
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  3. Mingyao Liu
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Correspondence to Mingyao Liu.

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Kim, H., Moodley, S. & Liu, M. TAT cell-penetrating peptide modulates inflammatory response and apoptosis in human lung epithelial cells. Drug Deliv. and Transl. Res. 5, 275–278 (2015). https://doi.org/10.1007/s13346-015-0230-6

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  • DOI: https://doi.org/10.1007/s13346-015-0230-6

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