title: Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL-8 production by alveolar epithelial cells in culture.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Texas Health Center, Department of Specialty Care Services, 119 37 US Highway 271, Tyler, Tx 75708, USA. ali.azghani@uthct.edu
authors.forename: A O
authors.initials: AO
authors.lastname: Azghani
authors.forename: J W
authors.initials: JW
authors.lastname: Baker
authors.forename: S
authors.initials: S
authors.lastname: Shetty
authors.forename: E J
authors.initials: EJ
authors.lastname: Miller
authors.forename: G J
authors.initials: GJ
authors.lastname: Bhat
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D016209:Interleukin-8; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; D010196:Pancreatic Elastase