title: Cell penetrating peptides fail to induce an innate immune response in epithelial cells in vitro: implications for continued therapeutic use.
abstract: Cell penetrating peptides (CPPs) offer the exciting potential of effectively delivering macromolecules to the cytoplasm of a cell that are otherwise impermeable to the plasma membrane. Although the use of these peptides has so far been well tolerated in clinical trials, it is important to remember that some of these CPPs were originally derived from pathogenic material. We therefore sought to determine if three of the most widely studied CPPs; HIV-TAT, Antennapedia and Transportan, initiated an immune response in epithelial cells. Using conditions where these peptides efficiently delivered a rhodamine tagged BSA cargo to the interior of epithelial cells, we failed to observe an effect on cell viability as determined by MTT assay (P>0.05). Further, CPP-mediated delivery of this protein cargo failed to activate NFκB, which would be indicative of toll-like receptor signalling. Finally, no significant increase in the release of the inflammatory cytokines interleukin (IL)-8 and IL-6 was detected in epithelial cells exposed to CPP complexes for 72 h (P>0.05). Together, these results indicate that these commonly used CPPs are passive carriers that do not initiate epithelial cell-associated 'danger signals' during the process of cytoplasmic delivery of a model protein cargo.
authors: Department of Pharmacy and Pharmacology, University of Bath, Bath, UK; Department of Biology and Biochemistry, University of Bath, Bath, UK.
authors: Edward
authors: E
authors: Carter
authors: Chun Yin
authors: CY
authors: Lau
authors: David
authors: D
authors: Tosh
authors: Stephen G
authors: SG
authors: Ward
authors: Randall J
authors: RJ
authors: Mrsny
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051943:Antennapedia Homeodomain Protein / Q000009:adverse effects / Q000737:chemistry; D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D029721:Drosophila Proteins / Q000009:adverse effects / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects*; D020895:Enterocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D019004:Galanin / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D007113:Immunity, Innate; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000009:adverse effects; D010446:Peptide Fragments / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism; D014862:Wasp Venoms / Q000009:adverse effects / Q000737:chemistry; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000737:chemistry
chemical_list: D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D057846:Cell-Penetrating Peptides; D016207:Cytokines; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; D009842:Oligopeptides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012235:Rhodamines; D014862:Wasp Venoms; D054322:tat Gene Products, Human Immunodeficiency Virus; C110068:transportan; D019004:Galanin
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; Antennapedia; CPP; Cell penetrating peptide; Epithelial; HIV-TAT; IL; Innate immunity; MTT; TNFα; Transportan; cell penetrating peptide; iPSC; induced pluripotent stem cell; interleukin; tumour necrosis factor α