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Published ahead of print on December 11, 2003, doi:10.1164/rccm.200207-765OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 645-653, (2004)
© 2004 American Thoracic Society

Cytokine Secretion by Cystic Fibrosis Airway Epithelial Cells

Marie N. Becker, Mariam S. Sauer, Marianne S. Muhlebach, Andrew J. Hirsh, Qi Wu, Margrith W. Verghese and Scott H. Randell

Cystic Fibrosis/Pulmonary Research and Treatment Center, Department of Medicine; Department of Cellular and Molecular Physiology; and Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Correspondence and requests for reprints should be addressed to Scott H. Randell, Ph.D., UNC CF Center, CB 7248, 4011 Thurston-Bowles, Chapel Hill, NC 27599. E-mail: randell{at}med.unc.edu

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-{kappa}B 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)-1ß–induced IL-8 or IL-6 secretion or nuclear factor-{kappa}B 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.




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