Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound
Autor: | Robert E. Barrow, David N. Herndon, J. R. Perez-Polo, Marcus Spies, Olivera Nesic |
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Rok vydání: | 2001 |
Předmět: |
Male
medicine.drug_class Injections Subcutaneous Genetic enhancement medicine.medical_treatment Gene Expression Statistics Nonparametric Anti-inflammatory Rats Sprague-Dawley Random Allocation Gene expression Genetics medicine Animals RNA Messenger Vector (molecular biology) Insulin-Like Growth Factor I Molecular Biology Liposome Burn wound integumentary system Tumor Necrosis Factor-alpha business.industry Genetic transfer Genetic Therapy Rats Cytokine Liposomes Immunology Cancer research Cytokines Molecular Medicine Burns business Interleukin-1 |
Zdroj: | Gene Therapy. 8:1409-1415 |
ISSN: | 1476-5462 0969-7128 |
DOI: | 10.1038/sj.gt.3301543 |
Popis: | The use of systemic IGF-1 has been shown to attenuate the postburn hypermetabolic response and improve burn wound healing. Local IGF-1 gene therapy, however, promotes re-epithelialization in the burn wound without the side-effects associated with systemic delivery. We tested the hypothesis that these beneficial effects are due to changes in local cytokine production. Adult male Sprague-Dawley rats received a 40% total body surface area full-thickness scald burn and randomly received a subcutaneous injection at the burn wound margin of saline or cationic liposomes containing a IGF-1 cDNA construct. Animals were killed at 1, 4, 7 and 10 days after burn trauma. Skin biopsies at the wound border were harvested for total RNA extraction. Cytokine mRNA expression was determined using a multi-probe RNase protection assay. Data are presented as means +/- s.e.m. Statistical analysis used the unpaired t-test or Mann-Whitney test where appropriate. Significance was accepted at P0.05. Treatment of the burn wound with liposomal IGF-1-cDNA transfer decreased IL-1beta mRNA levels on day 10 after burn trauma from five-fold burn-induced increases compared with sham-treated rats, to near the control values present in unburned skin samples. Similarly, there was an eight-fold increase in TNF-alpha mRNA expression on postburn day 10 that was abrogated by IGF-1 gene therapy. Local IGF-1 gene transfer attenuates the mRNA expression of the inflammatory cytokines IL-1beta and TNF-alpha in the burn wound. This change may improve burn wound healing by decreasing prolonged local inflammation. |
Databáze: | OpenAIRE |
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