Electroporation-mediated delivery of FER gene enhances innate immune response and improves survival in a murine model of pneumonia

Previously, we reported that electroporation-mediated (EP) delivery of the FER gene improved survival in a combined trauma-pneumonia model. The mechanism of this protective effect is unknown. In this paper, we performed a pneumonia model in C57/BL6 mice with 500 CFU of Klebsiella pneumoniae . After...

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Veröffentlicht in:	Gene therapy 2018-08, Vol.25 (5), p.359-375
Hauptverfasser:	Dolgachev, Vladislav, Panicker, Sreehari, Balijepalli, Sanjay, McCandless, Lane Kelly, Yin, Yue, Swamy, Samantha, Suresh, M. V., Delano, Matthew J., Hemmila, Mark R., Raghavendran, Krishnan, Machado-Aranda, David
Format:	Artikel
Sprache:	eng
Schlagworte:	13/21 13/31 14/63 38/1 38/90 42/41 45/29 631/1647/2300/1850 64/60 692/699/255 Alveoli Animal models Animals Bacteria Bacterial Load Biomedical and Life Sciences Biomedicine Brief Communication Care and treatment Cell Biology Containers Cytokines - metabolism Disease Models, Animal DNA binding proteins Drug resistance Electroporation Electroporation - methods Female Gene Expression Gene Therapy Gene transfer Genes Genetic aspects Genetic Therapy - methods Heat shock proteins Hsp90 protein Human Genetics Humans Immune clearance Immune response Immunity, Innate - genetics Infection Inflammation Innate immunity Inoculation Interleukin 1 Interleukin 1 receptor antagonist Interleukin 1 receptors Klebsiella pneumoniae - isolation & purification Lungs Methicillin Methicillin-Resistant Staphylococcus aureus - isolation & purification Mice Mice, Inbred C57BL Monocytes Murinae Nanotechnology Peroxidase Phagocytes Pneumonia Pneumonia, Bacterial - immunology Pneumonia, Bacterial - microbiology Pneumonia, Bacterial - therapy Protein-Tyrosine Kinases - administration & dosage Protein-Tyrosine Kinases - biosynthesis Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - immunology Staphylococcus aureus Staphylococcus infections Transcription (Genetics) Transcription factors Trauma Tumor Necrosis Factor-alpha - metabolism γ-Interferon
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Zusammenfassung:	Previously, we reported that electroporation-mediated (EP) delivery of the FER gene improved survival in a combined trauma-pneumonia model. The mechanism of this protective effect is unknown. In this paper, we performed a pneumonia model in C57/BL6 mice with 500 CFU of Klebsiella pneumoniae . After inoculation, a plasmid encoding human FER was delivered by EP into the lung (PNA/ p FER-EP). Survival of FER-treated vs. controls (PNA; PNA/EP- p cDNA) was recorded. In parallel cohorts, bronchial alveolar lavage (BAL) and lung were harvested at 24 and 72 h with markers of infection measured. FER-EP-treated animals reduced bacterial counts and had better 5-day survival compared to controls (80 vs. 20 vs. 25%; p
ISSN:	0969-7128 1476-5462
DOI:	10.1038/s41434-018-0022-y