C. M.P. Ribeiro and W. K. O’Neal Pages 872 - 882 ( 11 )
Chronic airway inflammation characterizes several airway diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The altered airway milieu that results from the pathogenic processes in these disorders affects the airway epithelia, leading to an up-regulation of their innate defense. In human airway epithelia, luminal inflammatory stimuli induce an adaptation characterized by an expansion of the endoplasmic reticulum (ER) and its Ca2+ stores. This epithelial adaption mediates Ca2+-dependent “hyperinflammatory” responses, and recent studies have shown that activation of the unfolded protein response (UPR) by ER stress is involved in the process. The UPR is also known to be activated by cigarette smoke, the primary trigger for development of COPD. These studies illustrate the functional role of UPR pathways during airway inflammation and suggest that targeting the UPR may be a therapeutic strategy for obstructive airway diseases. This article reviews the link between airway epithelial inflammation and activation of the UPR, and discusses how UPR activation might be relevant for CF and COPD airways disease.
Airway epithelia, airway inflammation, calcium stores, chronic obstructive pulmonary disease, cystic fibrosis, endoplasmic reticulum stress, unfolded protein response, airway infection, obstructive airway diseases, neutrophils, macrophages, protein synthesis, inflammatory mediators, homeostasis, transcription factor
Cystic Fibrosis/Pulmonary Research and Treatment Center and the Department of Medicine, The University of North Carolina at Chapel Hill, CB #7248, 7013 Thurston-Bowles Building, Chapel Hill, NC 27599-7248, USA.