Signaling intermediates required for NF-kappa B activation and IL-8 expression in CF bronchial epithelial cells

• Published in: American journal of physiology. Lung cellular and molecular physiology 2003-02, Vol.284 (2), p.307-L315
• Main Authors: Li, Jing, Johnson, Xa Dwight, Iazvovskaia, Svetlana, Tan, Alan, Lin, Anning, Hershenson, Marc B
• Format: Article
• Language: English
• Subjects: Antibodies - pharmacology; Bronchi - metabolism; Cell Line; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Enzyme Activation - physiology; Epithelial Cells - metabolism; G(M1) Ganglioside - immunology; Humans; I-kappa B Kinase; Interleukin-8 - genetics; Interleukin-8 - metabolism; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; Promoter Regions, Genetic - physiology; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction - physiology; Transcription, Genetic; Transcriptional Activation; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00086.2002

Department of Pediatrics and Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637 Ligation of the asialoGM1 Pseudomonas aeruginosa pilin receptor has been demonstrated to induce IL-8 expression in airway epithelial cells via an NF- B-dependent pathway. We examined the signaling pathways required for asialoGM1-mediated NF- B activation in IB3 cells, a human bronchial epithelial cell line derived from a cystic fibrosis (CF) patient, and C-38 cells, the rescued cell line that expresses a functional CF transmembrane regulator. Ligation of the asialoGM1 receptor with specific antibody induced greater IL-8 expression in IB3 cells than C-38 cells, consistent with the greater density of asialoGM1 receptors in CF phenotype cells. AsialoGM1-mediated activation of NF- B, I B kinase (IKK), and ERK was also greater in IB3 cells. With the use of genetic inhibitors, we found that IKK- and NF- B-inducing kinase are required for maximal NF- B transactivation and transcription from the IL-8 promoter. Finally, although ERK activation was required for maximal asialoGM1-mediated IL-8 expression, inhibition of ERK signaling had no effect on IKK or NF- B activation, suggesting that ERK regulates IL-8 expression in an NF- B-independent manner. asialoGM1; extracellular signal-regulated kinase; I B kinase; mitogen-activated protein kinase; mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase; nuclear factor- B-inducing kinase; tumor necrosis factor- ; cystic fibrosis