Effects of rewarming on nuclear factor-kappaB and interleukin 8 expression in cold-preserved alveolar epithelial cells.
| Autor: | Inoue K; Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan., Suzuki S, Kubo H, Ishida I, Ueda S, Kondo T |
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| Jazyk: | angličtina |
| Zdroj: | Transplantation [Transplantation] 2003 Jul 27; Vol. 76 (2), pp. 409-15. |
| DOI: | 10.1097/01.TP.0000076095.51697.5E |
| Abstrakt: | Background: Nuclear factor-kappaB (NF-kappaB) and interleukin (IL)-8 play important roles in the pathophysiology of acute lung injury after lung transplantation. Because alveolar epithelium is one of the most important sites at which IL-8 production takes place after reperfusion of donor lungs, we examined the effects of cold/rewarming on NF-kappaB and IL-8 expression in alveolar epithelial cells. Methods: A549 cells were preserved at 4 degrees C for 5 hr and then rewarmed for up to 20 hr. NF-kappaB was analyzed by electrophoretic mobility shift assay. IL-8 mRNA expression was examined by reverse transcription-polymerase chain reaction. IL-8 concentration in the cell culture medium after rewarming was measured by enzyme-linked immunosorbent assay. Results: NF-kappaB was increased in the nuclear extracts as early as 30 min after rewarming. There was a marked increase in the IL-8 mRNA expression at 1 and 3 hr after rewarming. IL-8 concentration in the cell culture medium was progressively increased during 20 hr following rewarming. The cell culture medium inhibited apoptosis of neutrophils significantly. The cold/rewarming-induced IL-8 production was reduced to approximately 50% by introducing an antisense oligonucleotide for the p65 subunit of NF-kappaB and by treatment with N-acetyl-leucinyl-leucinyl-norleucinal and pyrrolidine dithiocarbamate. The effect of dexamethasone treatment was dose dependent (reduced to approximately 30% at 10-5 M dexamethasone). Conclusions: Our results indicate that rewarming of cold-preserved alveolar epithelial cells itself may be an important initiator of the inflammatory cascades, including NF-kappaB activation and IL-8 release. Inhibition of NF-kappaB would be worth trying to control unnecessary IL-8 production and the inflammatory response in the donor lungs. |
| Databáze: | MEDLINE |
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