Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence

It is unclear whether inflammation in the cystic fibrosis (CF) lung relates predominantly to bacterial infection, or occurs as a direct consequence of mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein, Interleukin (IL)-8 secretion from CF and non-CF cell lines, and from CP and non-CP human primary nasal epithelial cells incubated with or without Pseudomonas aevuginosa, was measured. Activation of nuclear factor-KB (NF-KB) in unstimulated CF and non-CF nasal epithelial cells, cell lines and murine tissues was measured by gel-shift assays, No significant difference in basal IL-8 production or IVF-KB activation was observed between CF and non-CF primary nasal cells, However, CF cells exhibited a significantly (p<0.01) increased IL-8 secretion following P, aeruginosa stimulation. Equalization of the increased P, aeruginosa adherence observed in CF cells, to non-CP levels, resulted in comparable IL-8 secretion. Further, IL-8 production did not differ with mutations which result in either correctly localized CFTR, or in partial/total mislocalization of this protein, Similar levels of NF-KB activation mere observed in a number of organs of wildtype and CF mice. Finally, IL-8 secretion and NF-KB activity were not consistently increased in CF cell lines, Cos-7 cell transfection with plasmids expressing <Delta>F508 or G551D mutant CFTR protein resulted in increased activation of a p50-containing NF-kappaB complex, but IL-8 secretion was similar to mild-type cells. The authors conclude that the stimulus produced by Pseudomonas aeruginosa is the predominant inflammatory trigger in their models.