Interleukin (IL)-1β in tracheal aspirates from premature infants induces airway epithelial cell IL-8 expression via an NF-κB dependent pathway

Thomas K. Shimotake, Farzana M. Izhar, Kandelaria Rumilla, Jing Li, Alan Tan, Kristen Page, Allan R. Brasier, Michael D. Schreiber, Marc B. Hershenson

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)907-913
Number of pages7
JournalPediatric Research
Volume56
Issue number6
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Shimotake, T. K., Izhar, F. M., Rumilla, K., Li, J., Tan, A., Page, K., Brasier, A. R., Schreiber, M. D., & Hershenson, M. B. (2004). Interleukin (IL)-1β in tracheal aspirates from premature infants induces airway epithelial cell IL-8 expression via an NF-κB dependent pathway. Pediatric Research, 56(6), 907-913. https://doi.org/10.1203/01.PDR.0000145274.47221.10