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

Hisashi Oishi, Yoshinori Okada, Toshiaki Kikuchi, Yasushi Hoshikawa, Tetsu Sado, Masafumi Noda, Chiaki Endo, Akira Sakurada, Yuji Matsumura, Takashi Kondo

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)360-367
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number3
DOIs
Publication statusPublished - 01-03-2010

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Lung Transplantation
Interleukin-10
Interleukin-2
Allografts
Tumor Necrosis Factor-alpha
Inflammation
Gene Expression
Genes
Cytokines
Lipids
Galactosidases
Lung
Control Groups
Reverse Transcription
Edema
Plasmids
Necrosis
Transplantation
Hemorrhage
Escherichia coli

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Oishi, Hisashi ; Okada, Yoshinori ; Kikuchi, Toshiaki ; Hoshikawa, Yasushi ; Sado, Tetsu ; Noda, Masafumi ; Endo, Chiaki ; Sakurada, Akira ; Matsumura, Yuji ; Kondo, Takashi. / 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. In: Journal of Heart and Lung Transplantation. 2010 ; Vol. 29, No. 3. pp. 360-367.
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abstract = "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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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. / Oishi, Hisashi; Okada, Yoshinori; Kikuchi, Toshiaki; Hoshikawa, Yasushi; Sado, Tetsu; Noda, Masafumi; Endo, Chiaki; Sakurada, Akira; Matsumura, Yuji; Kondo, Takashi.

In: Journal of Heart and Lung Transplantation, Vol. 29, No. 3, 01.03.2010, p. 360-367.

Research output: Contribution to journalArticle

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

PY - 2010/3/1

Y1 - 2010/3/1

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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