Endoplasmic reticulum stress in chronic obstructive lung diseases.
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 Ca(2+) stores. This epithelial adaption mediates Ca(2+)-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.
Cystic Fibrosis/Pulmonary Research and Treatment Center, Chapel Hill, NC, USA. carla_ribeiro@med.unc.edu
C M P
CM
Ribeiro
W K
WK
O'Neal
D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology