Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines.

Cigarette smoking and aging are major risk factors for chronic obstructive pulmonary disease. An unsolved question is whether elderly lungs are particularly vulnerable to cigarette smoke (CS) exposure. In this study, we used a mouse model to test the hypothesis that aging increases the susceptibility to CS-induced pulmonary inflammation.

Decreased airway expression of vascular endothelial growth factor in cigarette smoke-induced emphysema in mice and COPD patients.

Vascular endothelial growth factor (VEGF) signaling is crucial for lung structure maintenance. Although VEGF deficiency plays a role in the pathogenesis of emphysema in animals, little is known about VEGF expression levels and functions, as well as VEGF receptors, in airway epithelial cells, which are in direct contact with the environment. In this study, C57BL/6J mice were exposed to cigarette smoke (CS) for short (approximately 10 days) and long (4-24 wk) time periods, and bronchiolar expressions of VEGF and its receptors VEGFR-1 and VEGFR-2 were examined.

Bronchiolar chemokine expression is different after single versus repeated cigarette smoke exposure.

Background: Bronchioles are critical zones in cigarette smoke (CS)-induced lung inflammation. However, there have been few studies on the in vivo dynamics of cytokine gene expression in bronchiolar epithelial cells in response to CS.

Methods: We subjected C57BL/6J mice to CS (whole body exposure, 90 min/day) for various periods, and used laser capture microdissection to isolate bronchiolar epithelial cells for analysis of mRNA by quantitative reverse transcription-polymerase chain reaction.

Human airway trypsin-like protease induces amphiregulin release through a mechanism involving protease-activated receptor-2-mediated ERK activation and TNF alpha-converting enzyme activity in airway epithelial cells.

Human airway trypsin-like protease (HAT), a serine protease found in the sputum of patients with chronic airway diseases, is an agonist of protease-activated receptor-2 (PAR-2). Previous results have shown that HAT enhances the release of amphiregulin (AR); further, it causes MUC5AC gene expression through the AR-epidermal growth factor receptor pathway in the airway epithelial cell line NCI-H292. In this study, the mechanisms by which HAT-induced AR release can occur were investigated.