Interleukin-8 production by cystic fibrosis nasal epithelial cells after tumor necrosis factor-alpha and respiratory syncytial virus stimulation.
High levels of neutrophils and the neutrophil-attracting chemokine interleukin (IL)-8 have been observed in the airways of patients with cystic fibrosis (CF). We hypothesized that CF respiratory epithelium produces excessive amounts of IL-8 either at baseline or after stimulation. To test this hypothesis we compared immunoreactive IL-8 release by primary nasal epithelial cell (NEC) cultures established from young children with or without CF, at several time points after stimulation of cultures with tumor necrosis factor-alpha (TNF-alpha) or infection with respiratory syncytial virus (RSV). Both stimuli induced significantly increased IL-8 release by both CF and control cultures. However, there was no difference between CF and control cells in either the magnitude or duration of the IL-8 response. The effect of transduction of CF cells with Ad5-CBCFTR, an adenovirus vector mediating expression of cystic fibrosis transmembrane regulator (CFTR), on IL-8 production was also determined. TNF-alpha stimulated IL-8 production was not different in Ad5-CBCFTR-transduced, -untransduced, or Ad5-CMVLacZ-transduced control cells. Lastly, immortalized CF tracheal epithelial cell lines, both uncorrected and retrovirally corrected with CFTR, were compared. Again, TNF-alpha-stimulated IL-8 production did not differ significantly between cell lines with and without functioning CFTR. Our data suggest that isolated CF NECs cultured under these conditions do not produce more IL-8 than do non-CF control cultures, either at baseline or after incubation with the nonspecific stimuli TNF-alpha and RSV. We conclude that the absence of functioning CFTR alone is not sufficient to cause excessive production of IL-8.
Black
H R
HR
Departments of Pediatrics and Internal Medicine, Division of Pulmonary Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Yankaskas
J R
JR
Johnson
L G
LG
Noah
T L
TL
D000256:Adenoviridae / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C505032:CFTR protein, human; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator