Cytokine secretion by cystic fibrosis airway epithelial cells.
It is controversial whether mutations in cystic fibrosis transmembrane conductance regulator intrinsically dysregulate inflammation. We characterized passage 2 human tracheobronchial epithelial cell cultures morphologically and physiologically and determined whether cytokine production or nuclear factor-kappaB activation was systematically altered in cystic fibrosis (CF) cells. Non-CF and CF cells originating from a total of 33 and 25 lungs, respectively, were available for culture on plastic or at an air-liquid interface until well differentiated. Forskolin-stimulated short-circuit currents were present in representative polarized non-CF cultures and were absent in CF cultures, whereas uridine 5'-triphosphate-stimulated currents were present in both. Constitutive or interleukin (IL)-1beta-induced IL-8 or IL-6 secretion or nuclear factor-kappaB activity was not significantly different between non-CF and CF cells. The cytokines regulated upon activation, normal T cell expressed and secreted (RANTES) and IL-10 were not detectable. Stimulation with tumor necrosis factor-alpha or a synthetic toll-like receptor 2 agonist or variable doses and times of Staphylococcus aureus culture filtrate revealed a single dose- and time-dependent difference in IL-8 production by CF cells. Interestingly, although IL-8 secretion after stimulation with Pseudomonas aeruginosa filtrates was not greater in CF cells in the absence of human serum, it was variably greater in its presence. Thus, although exaggerated responses may develop under certain conditions, our results do not support an overall intrinsically hyperinflammatory phenotype in CF cells.
Becker
Marie N
MN
Cystic Fibrosis/Pulmonary Research and Treatment Center, Department of Medicine, The University of North Carolina at Chapel Hill, 27599, USA.
Sauer
Mariam S
MS
Muhlebach
Marianne S
MS
Hirsh
Andrew J
AJ
Wu
Qi
Q
Verghese
Margrith W
MW
Randell
Scott H
SH
D000293:Adolescent; D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
C505032:CFTR protein, human; D018946:Chemokine CCL5; D016207:Cytokines; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D016753:Interleukin-10