Reduced interleukin-8 production by cystic fibrosis airway epithelial cells.
The acquisition of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) is the initial event leading to bronchiectasis and lung disease. Although the host factors that permit initial airway colonization are largely unknown, recent studies suggest that secretion of interleukin (IL)-8 by airway epithelia and local recruitment of neutrophils is the final pathway in a pulmonary cytokine network. To determine whether differences in cytokine production exist between normal and CF airway epithelia, secretion of immunoreactive IL-8 and IL-10 as well as specific messenger RNA (mRNA) abundance were compared in airway epithelia expressing normal and mutant CF transmembrane regulator. After induction with IL-1beta, a CF airway cell line engineered to express the wild-type CF gene (CFT1-LCFSN) secreted significantly more immunoreactive IL-8 than did its isogenic parent that expressed the mutant CF gene (CFT1) or an isogenic vector control line (CFT1-LC3). Further studies with the three related cell lines demonstrated that expression of CFT1-LCFSN was associated with a significant increase in uninduced secretion of immunoreactive IL-8 as well as a 10- to 20-fold increase in IL-8 mRNA abundance when compared with the isogenic lines expressing the mutant gene. IL-1beta induction and intracellular accumulation of IL-8 appeared to be unaffected by CF genotype. These studies suggest that IL-8 secretion by CF airway epithelial cells is defective and may contribute to Pseudomonas persistence in the CF airway. Further studies are needed to confirm this difference in other cell lines and determine the linkage between IL-8 production and CF gene expression.
Massengale
A R
AR
Departments of Pediatrics, Medicine, and Microbiology and Immunology, West Virginia University, Morgantown, West Virginia, USA.
Quinn
F
F
Yankaskas
J
J
Weissman
D
D
McClellan
W T
WT
Cuff
C
C
Aronoff
S C
SC
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002461:Cell Line, Transformed; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10