Targeted Deletion of Jun/AP-1 in Alveolar Epithelial Cells Causes Progressive Emphysema and Worsens Cigarette Smoke-Induced Lung Inflammation

The c-Jun/AP-1 transcriptional factor is known to regulate cell proliferation, apoptosis, and inflammatory responses; however its role in lung pathogenesis is largely unknown. Here we report that the declined expression levels of c-Jun mRNA and protein in the lung tissues of advanced chronic obstructive pulmonary disease (COPD) patients, and that genetic deletion of c-Jun specifically in alveolar epithelial cells causes progressive emphysema with lung inflammation and alveolar air space enlargement, which are cardinal features of emphysema. Although mice lacking c-Jun specifically in lung alveolar epithelial cells appear normal at 6 weeks of age, when exposed to chronic cigarette smoke, c-Jun mutant mice display more lung inflammation with perivascular and peribronchiolar infiltrates. These results demonstrate that the c-Jun/AP-1 pathway is critical for maintaining lung alveolar cell homeostasis and that loss of its expression can contribute to lung inflammation and progressive emphysema.