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

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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
Author(s): 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.
Abstract: 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.
Issue Date: 2012-02
Publisher: Elsevier
Citation Info: Reddy, N. M., Vegiraju, S., Irving, A., Paun, B. C., Luzina, I. G., Atamas, S. P., Biswal, S., Ana, N. A., Mitzner, W., & Reddy, S. P. 2012. Targeted Deletion of Jun/AP-1 in Alveolar Epithelial Cells Causes Progressive Emphysema and Worsens Cigarette Smoke-Induced Lung Inflammation. American Journal of Pathology, 180(2): 562-574. DOI: 10.1016/j.ajpath.2011.10.029
Type: Article
Description: NOTICE: this is the author’s version of a work that was accepted for publication in the American Journal of Pathology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in the American Journal of Pathology, Vol 180, Issue 2, Feb 2012. DOI: 10.1016/j.ajpath.2011.10.029
URI: http://hdl.handle.net/10027/8614
ISSN: 0002-9440
Sponsor: This work was funded by National Institute of Health grants: RO1-ES11863, RO1-HL66109 and RO3-HL96933 (to SPR), the Flight Attendant Medical Research Institute CIA-award (to SPR), and the NIEHS training grant ES007141 (to SV). We thank both Pathology Core of the ALI-SCCOR (P50-HL073994) and COPD-SCCOR (P50-HL084945) supported by Hopkins-NIEHS center for utilizing their facilities and services in the present study. We also thank Dr. Erwin Wagner for proving c-Junf/f mice and Dr. Brigid Hogan for providing SPC-Cre mice.
Date Available in INDIGO: 2012-08-21
 

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