Abstract
Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression are each increased in premature infants undergoing mechanical ventilation. We sought to determine the cytokines responsible for IL-8 expression in this context. Tracheal aspirates were collected from 18 mechanically ventilated premature infants. IL-8 protein abundance was high in tracheal aspirates from ventilated premature infants (mean, 5806 ± 4923 pg/mL). IL-1α (mean, 20 ± 6 pg/mL), IL-1β (mean 67 ± 46 pg/mL), and tumor necrosis factor (TNF)-α (mean, 8 ± 2 pg/mL) were also found. Incubation of tracheal aspirates with 16HBE14o- human bronchial epithelial cells increased IL-8 protein in both cell lysates and supernatants, as well as transcription from the IL-8 promoter. Aspirates also induced nuclear factor (NF)-κB activation. Mutation of the IL-8 promoter NF-κB site abolished aspirate-induced IL-8 transcription. Endotoxin concentrations in the tracheal aspirates were negligible and incapable of inducing IL-8 promoter activity. Finally, incubation of tracheal aspirates with a neutralizing antibody against IL-1β reduced epithelial cell IL-8 production, whereas neutralizing antibodies against IL-1α and TNF-α had no effect. We conclude that airway fluid from mechanically ventilated premature infants contains soluble factors capable of inducing airway epithelial cell IL-8 expression via a NF-κB-dependent pathway, and that IL-1β plays a specific role in this process.
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Abbreviations
- AP-1:
-
activator protein-1
- BPD:
-
bronchopulmonary dysplasia
- NF-κB:
-
nuclear factor-κB
- TNF-α:
-
tumor necrosis factor-α
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Acknowledgements
The authors thank Dr. Steven White for his gift of the 16HBE14o- bronchial epithelial cells, Dr. Marsha Rosner for her gift of pCMV-LacZ, and the University of Chicago Children's Hospital Neonatal Intensive Care Unit nurses for their assistance in collecting patient samples.
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Supported by National Institutes of Health Grant HL56399 and the Children's Research Foundation.
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Shimotake, T., Izhar, F., Rumilla, K. et al. Interleukin (IL)-1β in Tracheal Aspirates from Premature Infants Induces Airway Epithelial Cell IL-8 Expression via an NF-κB Dependent Pathway. Pediatr Res 56, 907–913 (2004). https://doi.org/10.1203/01.PDR.0000145274.47221.10
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DOI: https://doi.org/10.1203/01.PDR.0000145274.47221.10
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