Philippe Dje N'Guessan1, Helge Haarmann2, Tamara Steiner3, Kerstin Heyl4, Frauke Schreiber5, Annina Heinrich5, Hortense Slevogt6. 1. Department of Pulmonary and Critical Care Medicine, Red Cross Hospital, Stuttgart, Germany. 2. Department of Internal Medicine/Infectious Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany; Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. 3. Department of Internal Medicine/Infectious Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany; Neurological Rehabilitation Center for Children and Adolescents, Helios Klinikum Hohenstücken, Brandenburg, Germany. 4. Septomics Research Center, University Hospital Jena, Jena, Germany. 5. Department of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany. 6. Septomics Research Center, University Hospital Jena, Jena, Germany. Electronic address: hortense.slevogt@med.uni-jena.de.
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. CONCLUSION: 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.
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. CONCLUSION: The interaction between M. catarrhalis and EGFRincreases 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: Richa Singh; Alexander J Mackay; Anant Rc Patel; Davinder S Garcha; Beverly S Kowlessar; Simon E Brill; Louise E Donnelly; Peter J Barnes; Gavin C Donaldson; Jadwiga A Wedzicha Journal: Respir Res Date: 2014-09-14
Authors: Sudha Bhadriraju; Douglas W Fadrosh; Susan V Lynch; John Z Metcalfe; Meera K Shenoy; Din L Lin; Kole V Lynch; Kathryn McCauley; Rashida A Ferrand; Edith D Majonga; Grace McHugh; Laurence Huang Journal: Sci Rep Date: 2020-09-30 Impact factor: 4.996