Cystic Fibrosis/Pulmonary Research and Treatment Center, Chapel Hill, NC, USA.
Curr Mol Med. 2012 Aug;12(7):872-82. doi: 10.2174/156652412801318791.
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.
慢性气道炎症是几种气道疾病的特征，包括囊性纤维化 (CF) 和慢性阻塞性肺疾病 (COPD)。这些疾病的致病过程导致的气道微环境改变会影响气道上皮，导致其先天防御的上调。在人类气道上皮中，腔刺激性炎症刺激诱导以内质网 (ER) 及其 Ca(2+) 储存扩张为特征的适应性。这种上皮适应介导 Ca(2+)-依赖性“过度炎症”反应，最近的研究表明，内质网应激激活未折叠蛋白反应 (UPR) 参与了这一过程。UPR 也已知会被香烟烟雾激活，香烟烟雾是 COPD 发展的主要诱因。这些研究说明了 UPR 途径在气道炎症中的功能作用，并表明靶向 UPR 可能是阻塞性气道疾病的一种治疗策略。本文综述了气道上皮炎症与 UPR 激活之间的联系，并讨论了 UPR 激活如何与 CF 和 COPD 气道疾病相关。
