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Title: Targeted deletion of Jun/AP-1 in alveolar epithelial cells causes progressive emphysema and worsens cigarette smoke-induced lung inflammation.

Authors: Reddy, Narsa M; Vegiraju, Suryanaraya; Irving, Ashley; Paun, Bogdan C; Luzina, Irina G; Atamas, Sergei P; Biswal, Shyam; Ana, Navas-Acien; Mitzner, Wayne; Reddy, Sekhar P

Published In Am J Pathol, (2012 Feb)

Abstract: Chronic obstructive pulmonary disease appears to occur slowly and progressively over many years, with both genetic factors and environmental modifiers contributing to its pathogenesis. Although the c-Jun/activator protein 1 transcriptional factor regulates cell proliferation, apoptosis, and inflammatory responses, its role in lung pathogenesis is largely unknown. In this study, we report decreased expression levels of c-Jun mRNA and protein in the lung tissues of patients with advanced chronic obstructive pulmonary disease, and the 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 the age of 6 weeks, when exposed to long-term cigarette smoke, c-Jun-mutant mice display more lung inflammation with perivascular and peribronchiolar infiltrates compared with controls. These results demonstrate that the c-Jun/activator protein 1 pathway is critical for maintaining lung alveolar cell homeostasis and that loss of its expression can contribute to lung inflammation and progressive emphysema.

PubMed ID: 22265050 Exiting the NIEHS site

MeSH Terms: Aged; Animals; Antioxidants/metabolism; Cytokines/metabolism; Female; Gene Deletion*; Gene Expression/physiology; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Pneumonia/genetics; Proto-Oncogene Proteins c-jun/deficiency; Proto-Oncogene Proteins c-jun/genetics*; Proto-Oncogene Proteins c-jun/metabolism; Pulmonary Alveoli/metabolism; Pulmonary Disease, Chronic Obstructive/genetics*; Pulmonary Disease, Chronic Obstructive/metabolism; Pulmonary Emphysema/genetics*; Pulmonary Emphysema/metabolism; RNA, Messenger/metabolism; Respiratory Mucosa/metabolism; Smoke/adverse effects*; Smoking/adverse effects; Smoking/genetics; Transcription Factor AP-1/genetics*

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