Tumor necrosis factor-induced interleukin-8 expression in cultured human airway epithelial cells.
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.
Kwon
O J
OJ
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Au
B T
BT
Collins
P D
PD
Adcock
I M
IM
Mak
J C
JC
Robbins
R R
RR
Chung
K F
KF
Barnes
P J
PJ
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*
D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003513:Cycloheximide