Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines.
A tendency toward excessive inflammation in cystic fibrosis (CF) patients often accompanies lung infections with Pseudomonas aeruginosa. We tested the cytokine response to P. aeruginosa in two pairs of human airway epithelial cell lines matched except for CF transmembrane conductance regulator activity. The 9/HTEo(-) CF-phenotypic cell line produced significantly more interleukin (IL)-8, IL-6, and granulocyte-macrophage colony-stimulating factor but not regulated on activation normal T cell expressed and secreted (RANTES) in response to Pseudomonas than the 9/HTEo(-) control line, and the differences widened over time. Similarly, a 16HBE cell line lacking transmembrane conductance regulator activity showed enhanced IL-8 and IL-6 responses compared with the control cell line. The pharmacology of the cytokine response also differed because dexamethasone reduced cytokine production to similar levels in the matched cell lines. The protracted proinflammatory cytokine response of the CF-phenotypic cell lines suggests that the limiting mechanisms of normal cells are absent or attenuated. These results are consistent with in vivo observations in patients with CF and suggest that our novel cell lines may be useful for further investigation of the proinflammatory responses in CF airways.
Kube
D
D
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. dmk8@po.cwru.edu
Sontich
U
U
Fletcher
D
D
Davis
P B
PB
D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D018946:Chemokine CCL5 / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011552:Pseudomonas Infections / Q000378:metabolism*; D013997:Time Factors; D014132:Trachea / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology
C505032:CFTR protein, human; D018946:Chemokine CCL5; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D016376:Oligonucleotides, Antisense; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor