title: Tumor necrosis factor-induced interleukin-8 expression in cultured human airway epithelial cells.
abstract: The effects of tumor necrosis factor-alpha (TNF-alpha) on interleukin-8 (IL-8) expression and generation were examined in primary cultured human airway epithelial cells (HAEC) and a human lung epithelial cell line (A549). TNF-alpha increased IL-8 mRNA and protein expression in HAEC in a concentration- and time-dependent manner and these effects were inhibited by dexamethasone (1 microM). There was no change in the stability of IL-8 mRNA, and a nuclear run-on assay confirmed that TNF-alpha increased IL-8 gene transcription. TNF-alpha-induced IL-8 mRNA expression showed a biphasic response in HAEC, with an early increase at 2 h followed by a sustained increase from 8 h, which was abolished by the addition of cycloheximide, suggesting that the synthesis of another protein was involved. A549 cells also increased IL-8 secretion and mRNA after incubation of TNF-alpha, with inhibition by dexamethasone. However, A549 cells showed only an early single peak. A549 cells showed a 250-fold increase in the generation of IL-8 immunoreactivity, whereas primary cultured HAEC showed only a threefold increase, suggesting that HAEC and A549 cells may respond to TNF-alpha in different ways. The sustained increase in IL-8 secretion due to an increase in gene transcription in response to TNF-alpha may be an important amplification step in inflammatory diseases of the airways.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: O J
authors.initials: OJ
authors.lastname: Kwon
authors.forename: B T
authors.initials: BT
authors.lastname: Au
authors.forename: P D
authors.initials: PD
authors.lastname: Collins
authors.forename: I M
authors.initials: IM
authors.lastname: Adcock
authors.forename: J C
authors.initials: JC
authors.lastname: Mak
authors.forename: R R
authors.initials: RR
authors.lastname: Robbins
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003513:Cycloheximide