Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.
Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells.
Kwon
O J
OJ
Department of Thoracic Medicine, National Heart and Lung Institute, London, U.K.
Au
B T
BT
Collins
P D
PD
Baraniuk
J N
JN
Adcock
I M
IM
Chung
K F
KF
Barnes
P J
PJ
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D002648:Child; D003094:Collagen / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003094:Collagen