TY - JOUR
T1 - Transbronchial human interleukin-10 gene transfer reduces acute inflammation associated with allograft rejection and intragraft interleukin-2 and tumor necrosis factor-α gene expression in a rat model of lung transplantation
AU - Oishi, Hisashi
AU - Okada, Yoshinori
AU - Kikuchi, Toshiaki
AU - Hoshikawa, Yasushi
AU - Sado, Tetsu
AU - Noda, Masafumi
AU - Endo, Chiaki
AU - Sakurada, Akira
AU - Matsumura, Yuji
AU - Kondo, Takashi
N1 - Funding Information:
This work was supported, in part, by Grant-in-Aid for Scientific Research (No. 14370401 and No. 18591537 ) from Japan Society for the Promotion of Science .
PY - 2010/3
Y1 - 2010/3
N2 - Background: The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). This study examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on AR and the intragraft cytokine profile in a rat model of lung transplantation. Methods: Left single lung transplants were performed between a highly histoincompatible combination of inbred rats. The donor left lung was extracted and intrabronchially instilled with a plasmid encoding hIL-10 (IL-10 group) or Escherichia coli β-galactosidase (control group), mixed with a cationic lipid. At 3 and 6 days after transplantation, the degree of AR was graded histologically (stage 1-4) and several pathologic categories of inflammation were scored on a scale of 0 to 4 according to the percentage of involvement. Intragraft cytokine profile was examined by real-time reverse transcription polymerase chain reaction. Results: The stage of AR (3.1 ± 0.4 vs 3.8 ± 0.4) and the pathologic scores for edema (2.3 ± 0.8 vs 3.2 ± 0.4), intraalveolar hemorrhage (0.3 ± 0.5 vs 2.2 ± 0.8), and necrosis (0.3 ± 0.5 vs 1.2 ± 0.4) in the IL-10 group were significantly decreased compared with the control group at Day 6. IL-2 and tumor necrosis factor-α messenger RNA expression levels on Day 3 were significantly decreased in the IL-10 group. Conclusions: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR, which was related to decreased levels of proinflammatory cytokine gene expression in a rat model of lung transplantation.
AB - Background: The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). This study examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on AR and the intragraft cytokine profile in a rat model of lung transplantation. Methods: Left single lung transplants were performed between a highly histoincompatible combination of inbred rats. The donor left lung was extracted and intrabronchially instilled with a plasmid encoding hIL-10 (IL-10 group) or Escherichia coli β-galactosidase (control group), mixed with a cationic lipid. At 3 and 6 days after transplantation, the degree of AR was graded histologically (stage 1-4) and several pathologic categories of inflammation were scored on a scale of 0 to 4 according to the percentage of involvement. Intragraft cytokine profile was examined by real-time reverse transcription polymerase chain reaction. Results: The stage of AR (3.1 ± 0.4 vs 3.8 ± 0.4) and the pathologic scores for edema (2.3 ± 0.8 vs 3.2 ± 0.4), intraalveolar hemorrhage (0.3 ± 0.5 vs 2.2 ± 0.8), and necrosis (0.3 ± 0.5 vs 1.2 ± 0.4) in the IL-10 group were significantly decreased compared with the control group at Day 6. IL-2 and tumor necrosis factor-α messenger RNA expression levels on Day 3 were significantly decreased in the IL-10 group. Conclusions: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR, which was related to decreased levels of proinflammatory cytokine gene expression in a rat model of lung transplantation.
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U2 - 10.1016/j.healun.2009.10.002
DO - 10.1016/j.healun.2009.10.002
M3 - Article
C2 - 20202600
AN - SCOPUS:77349115744
SN - 1053-2498
VL - 29
SP - 360
EP - 367
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 3
ER -