Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL-8 production by alveolar epithelial cells in culture

• Published in: Inflammation research Vol. 51; no. 10; pp. 506 - 510
• Main Authors: Azghani, A O, Baker, J W, Shetty, S, Miller, E J, Bhat, G J
• Format: Journal Article
• Language: English
• Published: Switzerland Springer Nature B.V 01.10.2002
• Subjects: Animals; Blotting, Western; Cell Line; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Enzyme Activation - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; Interleukin-8 - biosynthesis; Mitogen-Activated Protein Kinases - biosynthesis; Pancreatic Elastase - pharmacology; Phosphorylation; Protein Tyrosine Phosphatases - metabolism; Pseudomonas aeruginosa - enzymology; Pulmonary Alveoli - cytology; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - metabolism; Rabbits; Signal Transduction - drug effects; Stimulation, Chemical
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/PL00012420

Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8.