title: The Moraxella catarrhalis-induced pro-inflammatory immune response is enhanced by the activation of the epidermal growth factor receptor in human pulmonary epithelial cells.
abstract: BACKGROUND
  Chronic lower airway inflammation is considered to be a major cause of pathogenesis and disease progression in chronic obstructive pulmonary disease (COPD). Moraxella catarrhalis is a COPD-associated pathogen causing exacerbations and bacterial colonization in the lower airways of patients, which may contribute to chronic inflammation. Increasing evidence suggests that the epidermal growth factor receptor (EGFR) modulates inflammatory processes in the human airways. The goal of this study was to investigate the role of EGFR in the M. catarrhalis-induced pro-inflammatory immune response in airway epithelial cells.
  
  
  METHODS
  The effects of inhibition and gene silencing of EGFR on M. catarrhalis-dependent pro-inflammatory cytokine expression in human primary bronchial epithelial cells (NHBEs), as well as the pulmonary epithelial cell lines BEAS-2B and A549 were analyzed. We also assessed the involvement of EGFR-dependent ERK and NF-κB signaling pathways.
  
  
  RESULTS
  The M. catarrhalis-induced pro-inflammatory immune response depends, at least in part, on the phosphorylation and activation of the EGF receptor. Interaction of M. catarrhalis with EGFR increases the secretion of pro-inflammatory cytokines, which is mediated via ERK and NF-κB activation.
  
  
  CONCLUSIONS
  The interaction between M. catarrhalis and EGFR increases airway inflammation caused by this pathogen. Our data suggest that the inhibition of EGFR signaling in COPD could be an interesting target for reducing M. catarrhalis-induced airway inflammation.
authors: Department of Pulmonary and Critical Care Medicine, Red Cross Hospital, Stuttgart, Germany.
authors: Philippe Dje
authors: PD
authors: N'Guessan
authors: Department of Internal Medicine/Infectious Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany; Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors: Helge
authors: H
authors: Haarmann
authors: Department of Internal Medicine/Infectious Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany; Neurological Rehabilitation Center for Children and Adolescents, Helios Klinikum Hohenstücken, Brandenburg, Germany.
authors: Tamara
authors: T
authors: Steiner
authors: Septomics Research Center, University Hospital Jena, Jena, Germany.
authors: Kerstin
authors: K
authors: Heyl
authors: Department of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors: Frauke
authors: F
authors: Schreiber
authors: Department of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors: Annina
authors: A
authors: Heinrich
authors: Septomics Research Center, University Hospital Jena, Jena, Germany. Electronic address: hortense.slevogt@med.uni-jena.de.
authors: Hortense
authors: H
authors: Slevogt
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D050296:Microbial Viability; D001936:Moraxella catarrhalis / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Chronic obstructive pulmonary disease; Epidermal growth factor receptor; Inflammation; Moraxella catarrhalis; Pulmonary epithelial cells