Interleukin (IL)-1 beta in tracheal aspirates from premature infants induces airway epithelial cell IL-8 expression via an NF-kappa B dependent pathway.
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-1 alpha (mean, 20 +/- 6 pg/mL), IL-1 beta (mean 67 +/- 46 pg/mL), and tumor necrosis factor (TNF)-alpha (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)-kappa B activation. Mutation of the IL-8 promoter NF-kappa B 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-1 beta reduced epithelial cell IL-8 production, whereas neutralizing antibodies against IL-1 alpha and TNF-alpha 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-kappa B-dependent pathway, and that IL-1 beta plays a specific role in this process.
Shimotake
Thomas K
TK
Department of Pediatrics, University of Chicago, Illinois 60637, USA.
Izhar
Farzana M
FM
Rumilla
Kandelaria
K
Li
Jing
J
Tan
Alan
A
Page
Kristen
K
Brasier
Allan R
AR
Schreiber
Michael D
MD
Hershenson
Marc B
MB
D002478:Cells, Cultured; D004731:Endotoxins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012121:Respiration, Artificial; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013396:Suction; D014132:Trachea; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha