Influence of Cystic Fibrosis Transmembrane Conductance Regulator on Gene Expression in Response to Pseudomonas aeruginosa Infection of Human Bronchial Epithelial Cells

• Published in: Infection and Immunity Vol. 73; no. 10; pp. 6822 - 6830
• Main Authors: Reiniger, Nina, Ichikawa, Jeffrey K, Pier, Gerald B
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01-10-2005
• Subjects: Bacteriology; Biological and medical sciences; Bronchi - cytology; Bronchi - microbiology; Cell Line; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Cytokines - genetics; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression; Host Response and Inflammation; Humans; Immunity, Innate - genetics; Microbiology; Miscellaneous; Mutation; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Oligonucleotide Array Sequence Analysis; Pneumonia, Bacterial - genetics; Pneumonia, Bacterial - immunology; Pseudomonas aeruginosa; Pseudomonas Infections - genetics; Pseudomonas Infections - immunology; Transmembrane protein; Pseudomonadales; Human; Microbiology; Bacteria; Pseudomonadaceae; Epithelial cell; Pseudomonas aeruginosa; Gene expression; Cystic fibrosis transmembrane conductance regulator; Immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.73.10.6822-6830.2005

Chronic lung infection by Pseudomonas aeruginosa causes significant morbidity in cystic fibrosis patients initiated by the failure of innate immune responses. We used microarray analysis and real-time PCR to detect transcriptional changes associated with cytokine production in isogenic bronchial epithelial cell lines with either wild-type (WT) or mutant cystic fibrosis transmembrane conductance regulator (CFTR) in response to P. aeruginosa infection. The transcription of four NF-[kappa]B-regulated cytokine genes was maximal in the presence of WT CFTR: the interleukin-8 (IL-8), IL-6, CXCL1, and intracellular adhesion molecule 1 (ICAM-1) genes. Analysis of protein expression in two cell lines paired for wild-type and mutant CFTR with three P. aeruginosa strains showed IL-6 and IL-8 expressions were consistently enhanced by the presence of WT CFTR in both cell lines with all three strains of P. aeruginosa, although some strains gave small IL-8 increases in cells with mutant CFTR. CXCL1 production showed consistent enhancement in cells with WT CFTR using all three bacterial strains in one cell line, whereas in the other cell line, CXCL1 showed a significant increase in cells with either WT or mutant CFTR. ICAM-1 was unchanged at the protein level in one of the cell lines but did show mild enhancement with WT CFTR in the other cell pair. Inhibitions of NF-[kappa]B prior to infection indicated differing degrees of dependence on NF-[kappa]B for production of the cytokines, contingent on the cell line. Cytokine effectors of innate immunity to P. aeruginosa were found to be positively influenced by the presence of WT CFTR, indicating a role in resistance to P. aeruginosa infection.