Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs

Makoto Ishii, Yukio Suzuki, Kei Takeshita, Naoki Miyao, Hiroyasu Kudo, Rika Hiraoka, Kazumi Nishio, Nagato Sato, Katsuhiko Naoki, Takuya Aoki, Kazuhiro Yamaguchi

研究成果: Article

58 引用 (Scopus)

抄録

Although c-Jun NH2-terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-κB-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4°C for 4 h followed by reperfusion at 37°C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-κB qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-α into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation.

元の言語English
ページ(範囲)2569-2577
ページ数9
ジャーナルJournal of Immunology
172
発行部数4
出版物ステータスPublished - 2004 2 15

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JNK Mitogen-Activated Protein Kinases
Reperfusion Injury
Transcription Factor AP-1
Lung
Lung Injury
Reperfusion
Lung Transplantation
Bronchoalveolar Lavage Fluid
Apoptosis
Ischemia
B-Form DNA
Alveolar Epithelial Cells
Extracellular Signal-Regulated MAP Kinases
Alveolar Macrophages
L-Lactate Dehydrogenase
Smooth Muscle Myocytes
Blood Vessels
Transplantation
Biomarkers
Proteins

ASJC Scopus subject areas

  • Immunology

これを引用

Ishii, M., Suzuki, Y., Takeshita, K., Miyao, N., Kudo, H., Hiraoka, R., ... Yamaguchi, K. (2004). Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs. Journal of Immunology, 172(4), 2569-2577.

Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs. / Ishii, Makoto; Suzuki, Yukio; Takeshita, Kei; Miyao, Naoki; Kudo, Hiroyasu; Hiraoka, Rika; Nishio, Kazumi; Sato, Nagato; Naoki, Katsuhiko; Aoki, Takuya; Yamaguchi, Kazuhiro.

:: Journal of Immunology, 巻 172, 番号 4, 15.02.2004, p. 2569-2577.

研究成果: Article

Ishii, M, Suzuki, Y, Takeshita, K, Miyao, N, Kudo, H, Hiraoka, R, Nishio, K, Sato, N, Naoki, K, Aoki, T & Yamaguchi, K 2004, 'Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs', Journal of Immunology, 巻. 172, 番号 4, pp. 2569-2577.
Ishii M, Suzuki Y, Takeshita K, Miyao N, Kudo H, Hiraoka R その他. Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs. Journal of Immunology. 2004 2 15;172(4):2569-2577.
Ishii, Makoto ; Suzuki, Yukio ; Takeshita, Kei ; Miyao, Naoki ; Kudo, Hiroyasu ; Hiraoka, Rika ; Nishio, Kazumi ; Sato, Nagato ; Naoki, Katsuhiko ; Aoki, Takuya ; Yamaguchi, Kazuhiro. / Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs. :: Journal of Immunology. 2004 ; 巻 172, 番号 4. pp. 2569-2577.
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abstract = "Although c-Jun NH2-terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-κB-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4°C for 4 h followed by reperfusion at 37°C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-κB qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-α into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation.",
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AU - Miyao, Naoki

AU - Kudo, Hiroyasu

AU - Hiraoka, Rika

AU - Nishio, Kazumi

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AU - Naoki, Katsuhiko

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AU - Yamaguchi, Kazuhiro

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