Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases.
Inhaled air is contaminated with pathogens and particulates that may deposit in the airways and damage the host. In response to these invaders, the airway epithelium has developed innate immune responses that provide a defence against the invaders and protect the airway structure and function. Thus, the epithelium of conducting airways becomes the "battleground" between the invaders and the host. Recent evidence suggests that airway epithelial surface signalling through the epidermal growth factor receptor (EGFR) is a convergent pathway producing innate immune responses to a variety of infectious and noninfectious noxious stimuli. In the present review, the EGFR signalling pathways leading to airway mucin production, neutrophil recruitment (via interleukin-8 production) and airway epithelial repair were examined. The importance of these findings in human airway diseases was also investigated. The current authors suggest that the exaggerated innate immune responses found in chronic inflammatory airway diseases (e.g. chronic obstructive pulmonary disease, cystic fibrosis and severe asthma) contribute to the pathogenesis or the aggravation of these diseases. Potential therapies include inhibition of the various elements of the described epidermal growth factor receptor cascade. In considering each therapeutic intervention, the potential benefits must be considered in relation to potential deleterious effects.
Burgel
P-R
PR
Service de Pneumologie and UPRES EA 2511, Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Nadel
J A
JA
D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D009077:Mucins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D016209:Interleukin-8; D008024:Ligands; D009077:Mucins; D017382:Reactive Oxygen Species; D066246:ErbB Receptors